UNIVERSITY OF VETERINARY AND
PHARMACEUTICAL SCIENCES BRNO
FACULTY OF PHARMACY
Department of Pharmaceutics
MEDICAL FORMS
AND BIOPHARMACY
I. Liquid and Semi-Solid Dosage Forms
Kateřina Dvořáčková
Aleš Franc
Jan Gajdziok
Martina Kejdušová
David Vetchý
BRNO 2014
3 UNIVERSITY OF VETERINARY A PHARMACEUTICAL
SCIENCES BRNO
FACULTY OF PHARMACY
Department of Pharmaceutics
MEDICAL FORMS AND BIOPHARMACY
I. Liquid and Semi-Solid Dosage Forms
Doc. PharmDr. Kateřina Dvořáčková, Ph.D.
PharmDr. Aleš Franc, Ph.D.
PharmDr. Jan Gajdziok, Ph.D.
PharmDr. Martina Kejdušová, Ph.D.
Doc. PharmDr. Mgr. David Vetchý Ph.D.
BRNO 2014
4 Content
1. 2. Liquid preparations ............................................................................................................ 6 1.1 Liquid preparations for oral use................................................................................... 6 1.2 Liquid preparations for cutaneous application .......................................................... 12 1.3 Pharmaceutical solutions ........................................................................................... 14 1.4 Syrups ........................................................................................................................ 29 1.5 Aromatic waters ......................................................................................................... 32 1.6 Mucilages................................................................................................................... 36 1.7 Herbal drug preparations ........................................................................................... 39 1.8 Eye drops ................................................................................................................... 46 1.9 Eye lotions ................................................................................................................. 57 1.10 Nasal drops............................................................................................................. 58 1.11 Ear drops ................................................................................................................ 62 1.12 Emulsions ............................................................................................................... 66 1.13 Suspensions ............................................................................................................ 76 Semi-solid preparations .................................................................................................... 86 2.1 Ointments................................................................................................................... 94 2.2 Creams ..................................................................................................................... 110 2.3 Gels .......................................................................................................................... 119 2.4 Pastes ....................................................................................................................... 123 5 PREFACE
The subject “Medical Forms and Biopharmacy” is offered in the curriculum of the
Pharmaceutical Faculty of the University of Veterinary and Pharmaceutical Sciences Brno
and taught by the Department of Pharmaceutics. Pharmaceutical technology is one of the
profile pharmaceutical disciplines, and it deals with the composition, formulation, production,
evaluation and quality assurance of drugs. It studies the conditions in which active substances
and pharmaceutical excipients are transformed into the final form of the medicinal product. It
also describes the various rules by which these processes are controlled, ensuring the
production of drugs maintains a level of declared efficiency, stability and safety. The
optimization of the technological process of drug production is as important a step as the
synthesis of active ingredients or the isolation of unknown compounds.
The main reason for the transformation of active substances into the form of medicinal
preparations is the requirement for a drug to be applied in safe and comfortable way, usually
by location and in a time-controlled manner.
The formulation and production of the final drug is often dependent upon pharmaceutical
excipients and their suitable selection. Constitutive excipients usually form the outer
appearance of the dosage form as well as its inner structure, and they control the application
of the drug, ensure the drug’s physico-chemical and microbiological stability, identify the
specific product and often regulate the sensory perception of the final product.
The identification of factors influencing the bioavailability of the active substance led to the
conclusion that medicine and its formulation play a key role in this issue. Pharmaceutical
technology, mainly due to the study of the relationship between the form of the medicinal
product and drug bioavailability, created a new way for the preparation of higher generation
drugs. Thus, an interdisciplinary field was created - biopharmacy, which combines knowledge
about chemically-defined active substances and their pharmacological properties with the
field of pharmaceutical technology, which deals with the formulation and design of
application forms. Together with the support of the modern knowledge of pharmacodynamics,
pharmacokinetics, chronopharmacology and pathophysiology, biopharmaceutical findings are
reflected in the development and production of drugs with a controlled and directed release.
6 The aim of these practical classes from subject Medical Forms and Biopharmacy is to try to
give students some basic information about the rules and techniques used in the field of
prepared dosage forms, both individually and industrially, with an emphasis on practical skills
training for the preparation and evaluation of liquid, semisolid and solid dosage forms in the
laboratory.
These manuscripts are based on the foundation of the Czech language version that extend and
complement with new knowledge and approaches. Emphasis is placed on trying to generalize
the national particularities of the level of European practices, which is closely connected with
the use of nomenclature, according to the European Pharmacopoeia.
5 1.
Liquid preparations
1.1
Liquid preparations for oral use
Liquid preparations for oral use are usually solutions, emulsions or suspensions containing
one or more active substances in a suitable vehicle; they may, however, consist of liquid
active substances used as such (oral liquids).
Some preparations for oral use are prepared by diluting concentrated liquid preparations, or
from powders or granules for oral solutions and suspensions, or for oral drops and syrups,
using a suitable vehicle.
The vehicle that is chosen for any preparation for oral use is dependant upon the nature of the
active substance(s) and shoud have organoleptic characteristics appropriate to the intended
use of the preparation.
Liquid preparations for oral use may contain suitable antimicrobial preservatives, antioxidants
and other excipients such as agents for dispersing, suspending, thickening, emulsifying,
buffering, wetting, solubilising, stabilising, flavouring, sweetening and for colour, authorised
by the administrative authority.
Emulsions may show evidence of phase separation but are readily redispersed upon shaking.
Suspensions may show sediment, which is readily dispersed upon shaking in order to have a
suspension that remains sufficiently stable to ensure that the correct dose is delivered.
Various categories of preparations:

Oral solutions, emulsions and suspensions.

Powders and granules for oral solutions and suspensions.

Oral drops.

Powders for oral drops.

Syrups.

Powders and granules for syrups.
6 Production
For the manufacturing, packaging, storage and distribution of liquid preparations for oral use,
suitable measures must be taken in order to retain their microbial quality; recommendations
on this aspect are provided in the text Microbiological Quality of Pharmaceutical
Preparations (Ph. Eur). In the manufacturing of liquid preparations for oral use contain
dispersed particles, measures are taken to ensure that there is a suitable and controlled particle
size with regard to the intended use.
During development, it must be demonstrated that a nominal content can be withdrawn from
the container for liquid preparations for oral use packaged in single-dose containers.
During the development of a preparation for oral use whose formulation contains an
antimicrobial preservative, the need for and the efficacy of the chosen preservative shall be
demonstrated to the satisfaction of the administrative authority. A suitable test method,
together with a criteria for judging the preservative properties of the formulation are provided
in the text, Efficacy of Antimicrobial Preservation (Ph. Eur).
Tests
Uniformity of dosage units. Solutions, suspensions and emulsions in single-dose containers
comply with the Test for Uniformity of Dosage Units (Ph. Eur) or, where justified and
authorised, with the test for uniformity of content or uniformity of mass shown below. Herbal
drugs and herbal drug preparations present in dosage form are not subject to the provisions of
this paragraph.
Uniformity of content. (Ph. Eur). Unless otherwise prescribed or justified and authorised,
single-dose suspension preparations comply with the following test: After shaking, empty
each container as completely as possible and carry out the test on the individual contents.
They comply with test B for uniformity of content of single-dose preparations.
Uniformity of mass. Single-dose preparations that are solutions or emulsions comply with
the following test: individually weigh the contents of 20 containers, emptied as completely as
possible, and determine the average mass. Not more than 2 of the individual masses may
deviate more than 10 per cent from the average mass and none may deviate more than 20 per
cent.
Dose and uniformity of dose of oral drops. , Introduce, by means of a dropping device, the
number of drops usually prescribed for one dose into a suitable graduated cylinder, or
introduce by means of a measuring device, the usually prescribed quantity. The dropping
speed can not exceed 2 drops per second. Weigh the liquid, repeat the addition, weigh again
7 and carry on repeating the additions and weighing until a total of 10 masses are obtained. No
single mass can deviates more than 10 per cent from the average mass. The total of 10 masses
should not differ more than 15 per cent from the nominal mass of 10 doses. If necessary,
measure the total volume of 10 doses. The volume can not differ more than 15 per cent from
the nominal volume of 10 doses.
Uniformity of mass of delivered doses from multidose containers (Ph. Eur). Liquid
preparations for oral use supplied in multidose containers comply with the test. Oral drops are
not subject to the provisions of this test.
Labeling
The label states the name of any added antimicrobial preservative.
Oral solutions, emulsions and suspensions
Definition
Oral solutions, emulsions and suspensions are supplied in single-dose or multidose containers.
Each dose from a multidose container is administered by means of a device suitable for
measuring the prescribed volume. The device is usually a spoon or a cup for volumes of 5 mL
or multiples thereof, or an oral syringe for other volumes.
Powders and granules for oral solutions and suspensions
Definition
Powders and granules for the preparation of oral solutions or suspensions generally conform
to the definitions in the monographs on Oral powders (Ph. Eur) or Granules (Ph. Eur) as
appropriate. They may contain excipients specifically to facilitate dispersion or dissolution,
and to prevent caking.
After dissolution or suspension, they comply with the requirements for oral solutions or oral
suspensions, as appropriate.
8 Tests
Uniformity of dosage units. Single-dose powders and single-dose granules comply with the
Test for Uniformity of Dosage Units (Ph. Eur) or, where justified and authorised, with the
tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and
herbal drug preparations present in dosage form are not subject to the provisions of this
paragraph.
Uniformity of content (Ph. Eur). Unless otherwise prescribed, justified and authorised,
single-dose powders and single-dose granules containing an active substance of less than 2
mg or less than 2 per cent of the total mass, must comply with test B for uniformity of content
of single-dose preparations. If the preparation has more than one active substance, the
requirement applies only to those substances that correspond to the above conditions.
Uniformity of mass (Ph. Eur). Single-dose powders and single-dose granules must comply
with the test for uniformity of mass of single-dose preparations. If the test for uniformity of
content is prescribed for all the active substances, the test for uniformity of mass is not
required.
Labelling
The label must state:
 the method of preparation of the solution or suspension,
 the conditions and the duration of storage after reconstitution.
Oral drops
Definition
Oral drops are solutions, emulsions or suspensions that are administered in small volumes
such as drops by means of a suitable device.
Labelling
The label states the number of drops per millilitre of preparation or per gram of preparation if
the dose is measured in drops.
9 Powders for oral drops
Definition
Powders for the preparation of oral drops generally conform to the definition of Oral powders
(Ph. Eur). They may contain excipients to facilitate dissolution or suspension in the prescribed
liquid, or to prevent caking.
After dissolution or suspension, they must comply with the requirements for oral drops.
Tests
Uniformity of dosage units. Single-dose powders for oral drops must comply with the test
for uniformity of dosage units (Ph. Eur) or, where justified and authorised, with the tests for
uniformity of content and/or uniformity of mass shown below. Herbal drugs and herbal drug
preparations present in dosage form are not subject to the provisions of this paragraph.
Uniformity of content. (Ph. Eur) Unless otherwise prescribed or justified and authorised,
single-dose powders for oral drops containing an active substance of less than 2mg or less
than 2 percent of the total mass, must comply with test B for uniformity of content of singledose preparations. If the preparation has more than one active substance, the requirement
applies only to those substances that correspond to the above conditions.
Uniformity of mass. (Ph. Eur). Single-dose powders for oral drops must comply with the test
for uniformity of mass of single-dose preparations. If the test for uniformity of content is
prescribed for all the active substances, the test for uniformity of mass is not required.
Syrups
Definition
Syrups are aqueous preparations characterised by a sweet taste and a viscous consistency.
They may contain sucrose at a concentration of at least 45 percent m/m. The sweet taste can
also be obtained by using other polyols or sweetening agents. Syrups usually contain aromatic
or other flavouring agents. Each dose from a multidose container is administered by means of
a device suitable for measuring the prescribed volume. The device is usually a spoon or a cup
for volumes of 5 mL or multiples thereof.
Labelling
The label must state the name and concentration of the polyol or sweetening agent.
10 Powders and granules for syrups
Definition - Powders and granules for syrups generally conform to the definitions in the
monograph on Oral powders (Ph. Eur) or Granules (Ph. Eur). They may contain excipients to
facilitate dissolution. After dissolution, they must comply with the requirements for syrups.
Tests
Uniformity of dosage units. Single-dose powders and granules for syrups must comply with
the test for uniformity of dosage units (Ph. Eur) or, where justified and authorised, with the
tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and
herbal drug preparations present in dosage form are not subject to the provisions of this
paragraph.
Uniformity of content (Ph. Eur). Unless otherwise prescribed, justified and authorised,
single-dose powders and granules for syrups containing an active substance of less than 2 mg
or less than 2 per cent of the total mass comply with test B for uniformity of content of singledose preparations. If the preparation has more than one active substance, the requirement
applies only to those substances that correspond to the above conditions.
Uniformity of mass (Ph. Eur). Single-dose powders and granules for syrups must comply
with the test for uniformity of mass of single-dose preparations. If the test for uniformity of
content is prescribed for all the active substances, the test for uniformity of mass is not
required.
11 1.2
Liquid preparations for cutaneous application
Liquid preparations for cutaneous application are preparations consisting of a variety of
viscosities intended for the local or transdermal delivery of active ingredients. They are
solutions, emulsions or suspensions that may contain one or more active substances in a
suitable vehicle. They may contain suitable antimicrobial preservatives, antioxidants and
other excipients such as stabilisers, emulsifiers and thickeners.
Emulsions may show evidence of phase separation, but are readily redispersed upon shaking.
Suspensions may contain sediment that is readily dispersed upon shaking to produce a
suspension that is sufficiently stable to enable a homogeneous preparation to be delivered.
Where applicable, containers for liquid preparations for a cutaneous application must comply
with the requirements of Materials used for the manufacture of containers (Ph. Eur.) and
Containers (Ph. Eur.).
When liquid preparations for cutaneous applications are dispensed in pressurised containers,
the containers must comply with the requirements of the monograph on Pressurised
pharmaceutical preparations (Ph. Eur.).
Preparations specifically intended for use on severely injured skin must be sterile.
There are several categories of liquid preparations for cutaneous application. For example:
 Shampoos,
 Cutaneous foams.
Production
During development, it must be demonstrated that a nominal content can be withdrawn from
the container of liquid preparation for cutaneous application presented in single-dose
containers.
In the manufacturing of liquid preparations for cutaneous application which contains
dispersed particles, measures must be taken to ensure a suitable and controlled particle size
with regard to the intended use.
In the manufacturing, packaging, storage and distribution of liquid preparations for cutaneous
application, suitable measures must also be taken to ensure their microbial quality.
Recommendations on this aspect are provided in the text Microbiological quality of
pharmaceutical preparations (Ph. Eur).
12 Sterile liquid preparations for cutaneous application are prepared using materials and methods
designed to ensure sterility and to avoid the introduction of contaminants and the growth of
micro-organisms. Recommendations on this aspect are provided in the text Methods of
preparation of sterile products (Ph. Eur).
During the development of liquid preparations intended for cutaneous application whose
formulation contains an antimicrobial preservative, the need for and the efficacy of the chosen
preservative shall be demonstrated to the satisfaction of the administrative authority. A
suitable test method, together with criteria for judging the preservative properties of the
formulation are provided in the text Efficacy of antimicrobial preservation (Ph. Eur).
Tests
Sterility (Ph. Eur). Where the label indicates that the preparation is sterile, it has complied
with the test for sterility.
Storage
If the preparation is sterile, it must be stored in a sterile, airtight, tamper-proof container.
Labelling
The label must state:
 The name of any added antimicrobial preservative;
 Where applicable, that the preparation is sterile.
Shampoos
Definition
Shampoos are liquid, or occasionally, semi-solid preparations intended for application to the
scalp and the subsequent rinsing with water. When rubbed with water they usually form a
lather.
They can be emulsions, suspensions or solutions. Shampoos normally contain surface active
agents.
Cutaneous foams
13 1.3
Pharmaceutical solutions
Solutions are some of the oldest dosage forms used in the treatment of patients, and the
compounding of solutions retains an important place in therapeutics at the present.
Solutions can be defined as a homogenous one-phase system consisting of two or more
components:
Solvent (dispersing compound) - determines the phase of the solution and usually constitutes
the largest proportion of the system, but there are some exceptions, such as syrups.
Solute (dissolved compound) - dispersed as molecules or ions throughout the solvent; i.e. they
are considered to be dissolved in the solvent.
Solutions may exist in any phase, but from a pharmaceutical standpoint, there are liquid
formulations that contain one or more chemical substances dissolved in a suitable solvent or
mixture of mutually miscible solvents. Generally, water is chosen as the vehicle in which
active ingredients (APIs) are dissolved because it is non-toxic, non-irritant, tasteless,
relatively cheap and many substances are water-soluble. In cases where drugs are not
particularly water-soluble or suffer from hydrolysis in an aqueous medium, other solvents are
used (hydrophilic - ethanol, glycerol, propylenglycol, PEG; hydrophobic - liquid paraffin,
natural and synthetic oils, ether, chloroform, benzene). Solutions can also contain other
excipients, such as solubilizators, antimicrobial agents (preservatives), antioxidants, buffers
and isotonicity modifiers, emulsifiers, viscosity increasing agents (thickeners), flavouring
agents, colours and perfumes, and absorption enhancers.
Solutions are popular due to their simplicity and the speed of their preparation, along with
many other advantages.
Advantages of solutions
 Easy to dose from concentrate by simple dilution
 Easy to mix if necessary
 Easy to measure accurately
 Easy to administer orally (acceptable for paediatric and geriatric use)
 Administration by any route
14  More quickly effective than tablets and capsules (fast therapeutic response)
 Homogenous (give uniform dose)
 Reduce irritation to the gastric mucosa
Disadvantages
 Less stable than solid dosage forms
 Bulky, therefore difficult to transport
 Solubility may be limited
 Need to mask taste or odours (oral)
 Need an accurate spoon to measure the dose
 Fragile packaging
 Microbial contamination is more likely
Solubility
Solubility is defined as the rate of dissolution of solids in liquid (for liquid ingredients it is a
measure of their mutual miscibility). This value could be quantitatively expressed as the
concentration of a saturated solution at a certain temperature (pharmacopoeias characterize
the solubility usually by words i.e. very soluble – practicaly insoluble). Solubility depends on
temperature, pressure, the nature of the solutes and solvents (similia similibus solventur), the
pH of the solution, the presence of common ions and the presence of other excipients
(electrolytes, solubilizators, etc.).
Solubility can be improved by physical or chemical means:
 Physical solubility improvement (used as processing step in pharmaceutical
technology):
o Co-solvents: non-aqueous solvents miscible with water, having a lower surface
tension than water (eg. ethanol, glycerol, propylene glycol).
o Complexation: two basic procedures (using cyclodextrines – molecular
inclusions or poly-iodine complexes creation) are used.
15 o Hydrotropism: distress of the associated water structure by extensive ions
(sodium benzoate, sodium acetate, etc.).
o Micellar solubilization: solubilized substance enters the colloidal micelles of
surfactants.
 Chemical solubility improvement (chemical modification of active substance):
o Creating more soluble salts
o Creating prodrugs: the preparation of inactive compounds (with better physicochemical properties) that must undergo biotransformation (bioactivation) in the
body (enzymatic x non-enzymatic) in order to have therapeutical activity
According to the pharmacopoiea the solutions could be used both topically and systemically.
Classification of pharmaceutical solutions
 Sterile solutions
o Parenterals (injections, infusions)
o Eye – ocular – ophthalmic (drops, rinses)
o Solutions designed for wounds, seriously damaged skin and mucous membrane
administration
o Solutions for peritoneal dialysis, irrigation of body cavities and surfaces of
open wounds (e.g. surgical operations)
 Solutions for local administration (topical) and for the administration into the
respiratory tract
o Nose and ear instilations, drops, sprayes, rinses
o Dermal solutions – liquida cutanea
Medicinal solutions
Aromatic waters and spirits
Mucilages
Shampoos
Collodions
16 Douches
 Oral and vaginal solutions
o Oral – oromucosalia
Gargles – gargarismatae
Oral rinses, mouthwashes – aquae gingivales
Solutions for gum treatment – solutiones gingivales
Oral solutions – solutiones oromucosales
o Vaginal
 Peroral and rectal solutions
o Peroral
Medicinal solutions (also in the form of drops)
Aromatic waters and spirits
Syrups
Mucilages (gels)
Elixirs
o Rectal
Preparations for cleansing, diagnosis or therapeutic reasons (enemas)
General methods of preparation
There are 4 basic possibilities for preparing pharmaceutical solutions:
1. Dissolving at a normal (laboratory) temperature.
2. Dissolving at a higher temperature.
3. Dissolving by using substances for improving solubility.
4. Preparing by chemical reaction.
Packaging
Packaging is specific for each type of preparation and administration route.
17 Usually small bottles are used, with or without a dropper, made from various material (glass –
heavy, innert; plastic – PVC, PE), either coloured (photosensitive substances) or transparent.
Labels
 Basic labels
o Colour (white – peroral, injection; red – oral, topical; yellow – laboratory
reagents)
o Label requirements (information for patient, dosage, date, adress of pharmacy,
signature, expiration, amount)
 Additional labels - important notices
Corrosive! Flammable! Shake before use! Only for animals! Poison!
Storing conditions (Keep away from light!; Keep in cold!)
Shelf life
 Specifies the pharmacist with respect to:
o National authorities’ recomandations
o Scientific literature
o Physico-chemical and microbiological stability
o Duration of therapy
For the most of the prepared pharmaceutical solutions, the maximum shelf life is 1 month if
protected antimicrobially (preservatives) or prepared from non-aqueous solvents,
and only 1 week for a antimicrobially non-protected water solution (2 weeks if stored in cold
conditions).
1. Dissolving at a normal (laboratory) temperature
a) Dissolution of active ingredients in adequate amounts of the specified solvent.
b) Solution mixing.
c) Filtration.
18 If there is more than 1 substance in the prescription to be dissolved, each substance should be
dissolved in a separate amount of the solvent, and the partial solutions should be mixed.
If there are more solvents in prescription, each substance should be dissolved in a solvent in
which it is best soluble, and the partial solutions should be mixed.
Volatile substances or liquids must be added at the end of the process.
EXAMPLES
 Exercise 1.3.1
Ammoniae solutio 10% - Ammonia solution 10%
Ammoniae solutio concentrata
Aqua purificata
19.25
30.75
Preparation procedure: Mix both liquids together and filtrate, while working in the fume hood
(ammonia vapors are irritating).
Additional labels on package: Corrosive!
Storage conditions: Store at temperature < 20°C
 Exercise 1.3.2
Calcii chloridi solutio – Calcium chloride solution
Calcii chloridum hexahydricum
Aqua purificata
25.0
25.0
Preparation procedure: Dissolve calcium chloride in purified water; mix and filtrate the blend.
 Exercise 1.3.3
Camphorae spiritus – Camphorated alcohol
Camphora racemica
Ethanolum 96% (V/V)
Aqua purificata
2.50
14.25
8.25
Preparation procedure: Dissolve camphor in ethanol. Add water gradually. Filtrate the
solution.
19 Additional labels on package: Flammable!
Storage conditions: Cold area (8-15°C), Keep away from light!
Shelf life: 3 months
Notes: Preparations with acontent of ethanol  40% can be marked as „Flammable!“
Preparations with content of ethanol higher than 60% or with content of ether in any
concentration must be labeled as „Flammable!“.
Preparations containing more than 20% of ethanol or other non-water solvents are
antimicrobialy protected (prolonged shelf life).
 Exercise 1.3.4
Solutio Castellani sine fuchsino – Castellani solution without fuchsin
Acidum boricum
Phenolum
Resorcinolum
Acetonum
Ethanolum 96%
Aqua purificata
0.8
3.6
8.0
4.0
7.4
76.2
Preparation procedure: Dissolve phenol and resorcinol in a mixture of ethanol and acetone.
Add a water solution of boric acid and filtrate the solution.
Storage conditions: Keep away from light!
Do not issue without a prescription!
Notes: Crystalline phenol may be replaced by liquid phenol (Phenolum liquefactum)
110 g liquid phenol = 100 g phenol + 10 g H2O
If the preparation contains photosensitive substance, the product must be kept in a dark
(brown) glass bottle.
20  Exercise 1.3.5
Solutio Fraeser – Fraeser‘s solution
Acidum benzoicum
Acidum salicylicum
Iodi solutio ethanolica
Camphorae spiritus
1.35
1.35
6.75
40.55
Preparation procedure: Dissolve benzoic and salicylic acid in camphorated alcohol. Add an
ethanolic iodine solution.
Additional labels on package: Flammable!, Keep away from light!
Storage conditions: The product must be kept in dark (brown) glass bottle so as not to react
with the iodine.
 Exercise 1.3.6
Solutio Galli-Valerio - Galli-Valerio solution
Phenolum
Glycerolum 85%
Natrii tetraboras decahydricus
Formaldehydi solutio 35%
Aqua purificata
0.5
1.5
1.5
2.5
ad 100.0
Preparation procedure: Dissolve sodium tetraborate in approximately 90g of purified water.
Add glycerol, a formaldehyde solution and phenol (liquid phenol). Add the rest of water up to
100g. Mix the blend and filtrate the solution.
Additional labels on package: Keep away from light!
Notes: Crystalline phenol could be replaced by liquid phenol (Phenolum liquefactum).
21  Exercise 1.3.7
Spiritus ethereus – Ether alcohol (= Guttae Hoffmani)
Ether solvens
Ethanolum 85%
6.25
18.75
Preparation procedure: Mix ether with ethanol.
Additional labels on package: Flammable!
Storage conditions: The product must be kept in dark bottle at a temperature between 8 and
15°C.
 Exercise 1.3.8
Rp.
Kalii iodidi
Aquae purificatae
2.5
ad 100.0
M.f.sol.
D.S. 3 x 1 spoonful
Preparation procedure: Dissolve potassium iodide in water. Filtrate the solution.
 Exercise 1.3.9
Rp.
Tannini
Aquae purificatae
1.0
ad 100.0
M.f.sol.
D.S. Linning.
Preparation procedure: Dissolve tannin in water.
22  Exercise 1.3.10
Rp.
Argenti nitratis
Aquae purificatae
0.1
ad 10.0
M.f.sol.
D.S. Dotting of the base of the leg ulcers
Sub signo veneni! Ad manus medici!
Preparation procedure: Dissolve silver nitrate in water. Filtrate the solution.
Notes: Silver nitrate is a photosensitive substance. Silver ions show a great willingness to be
reduced to metallic silver-black, so if the silver nitrate contaminates your clothing or skin it
can result in bad staining.
2. Dissolving at a higher temperature
a) Addition of API to the warmed solvent.
b) The dissolving of API by continual mixing or by quick boiling in water bath or cooker.
c) Supplement of evaporating solvent. Filtration of cooled solution.
If there are substances in formulas which do not need higher temperatures for dissolving, they
should be added to the cooled solution at the end of the preparation process or they should be
dissolved in part of the solvent at a normal temperature.
Volatile or thermolabile substances must be added at the end of the process to a cooled
solution.
Volatile solvents must be warmed in a water bath, not in a cooker or a fire!
23 EXAMPLES
 Exercise 1.3.11
Acidi borici solutio 3% - Solution of 3% boric acid
Acidum boricum
Aqua purificata
3.0
97.0
Preparation procedure: Dissolve boric acid in water heated to 60-70°C. Filtrate the solution.
Storage conditions: The product must be kept at a temperature between 8 and 15°C.
 Exercise 1.3.12
Aqua conservans – Preservation water
Methylparabenum
Propylparabenum
Aqua purificata
0.067
0.033
99.900
Preparation procedure: Dissolve the prescribed amount of methyl- and propylparaben
(analytical balances) in boiling water. Boil for 10 minutes. Supplement the evaporated water
after cooling. Filtrate the solution.
Additional labels on package: Keep away from light!
Notes: Addition of Aq. conservans to preparation is necessary to market on the label by c.p.
abbreviation (presence of parabens).
 Exercise 1.3.13
Natrii tetraboratis solutio glycerolica – Glycerolic solution of sodium tetraborate
Natrii tetraboratis
Glycerolum 85%
5.0
45.0
Preparation procedure: Dissolve sodium tetraborate in glycerol in a close-neck bottle by
heating on water bath.
24 Exercise 1.3.14
Solutio Jarisch – Solution of Jarisch
Acidum boricum
Glycerolum 85%
Aqua purificata
2.0
4.0
94.0
Preparation procedure: Dissolve boric acid in boiling purified water. Add glycerol after
cooling. Supplement the evaporated water. Filtrate the solution.
Shelf life: 1 month (parabens – microbiologicaly stable)
Notes: Addition of Aq. conservans
must be market on the label by c.p. abbreviation
(presence of parabens).
 Exercise 1.3.15
Rp.
Ethacridinii lactatis
Aquae purificatae
1.0
ad 100.0
M.f.sol.
D.S.: 1 spoonful into a glass of water for lavage of the oral cavity.
Preparation procedure: Dissolve ethacridine lactate at a high temperature (water bath) in
purified water by continual mixing until the solution turns yellow.
Shelf life: 3 weeks
Additional labels on package: Keep away from light!
25 3. Dissolving by using substances that improve solubility
The basic preparation procedure consists of mixing API with a substance that improves
solubility immediately before dissolving, or dissolving API in solution of solvent and a
substance which improves solubility.
EXAMPLES
 Exercise 1.3.16
Iodi solutio aquosa – Water iodine solution
Iodum
Kalii iodidum
Aqua purificata
1.0
2.5
96.5
Preparation procedure: Dissolve potassium iodide (excipient) in 2.5g of purified water to get a
50% KI solution. Dissolve 1.0g of iodine (API) in a KI solution. Add water up to 100.0g.
Storage conditions: The product must be kept in a dark (brown) glass bottle which does not
react with iodine.
 Exercise 1.3.17
Iodi solutio glycerolica - Glycerolic iodine solution
Iodum
Kalii iodidum
Aqua purificata
Glycerolum 85%
0.25
2.50
2.50
19.75
Preparation procedure: Dissolve potassium iodide (excipient) in purified water to get a 50%
KI solution. Dissolve 0.25g of iodine (API) in a KI solution. Add glycerol up to 25.0g. Filtrate
the solution.
Storage conditions: The product must be kept in a dark (brown) glass bottle that does not react
with iodine.
26  Exercise 1.3.18
Iodi solutio ethanolica - Ethanolic iodine solution
Iodum
Kalii iodidum
Aqua purificata
Ethanolum 96%
1.3
0.5
1.7
16.5
Preparation procedure: Dissolve potassium iodide (excipient) in purified water to get a
concentrated KI solution. Ad 1.3g of iodine (API) to the KI solution. Add ethanol up to 20.0g.
Filtrate the solution.
Storage conditions: The product must be kept in adark (brown) glass bottle that does not react
with iodine.
Additional label: Flammable!
 Exercise 1.3.19
Rp.
Mentholi
Ethanoli 96%
Polysorbati 80
Aquae purificatae
0.1
1.0
1.0
ad 100.0
M.f.sol.
D.S. Liniment.
Preparation procedure: Dissolve menthol in ethanol (co-solvent). Mix with polysorbate
(surfactant) in mortar. Add water. Filtrate the solution.
4. Preparing by chemical reaction
There is a defined specific procedure for each preparation.
27 EXAMPLES
 Exercise 1.3.20
Calcii hydroxidi solutio – Solution of calcium hydroxide
Calcii oxidum
Aqua purificata
1.0
q.s.
Preparation procedure: Sprinkle crushed calcium oxide in a ceramic bowl with approximately
4ml of boiled, purified water. Pour the resulting suspension into a bottle (100ml bottle of clear
glass), add 50ml of purified water, shake it vigorously and allow it to stand for approximately
1 hour. Decante the clear supernatant, remain in the bottle only solid calcium hydroxide and
fill it by 100ml of water, thoroughly shake the bottle and close it. Decante the fluid above the
supernatant without shaking just before use.
Storage conditions: The product should be stored in a completely filled and sealed container
resistant to alkalies.
Notes: Freshly boiled purified water (free of carbon dioxide) must be used for the preparation.
The preparation must be stored with the precipitate to provide a useful consistant
concentration of calcium hydroxide in the solution.
 Exercise 1.3.21
Spiritus saponis kalini – Alcohol with potassium soap
Kalii hydroxidum
Lini oleum
Ethanolum 96%
Aqua purificata
Lavandulae etheroleum
2.00
8.75
7.50
6.50
0.25
Preparation procedure: Dissolve potassium hydroxide in 3 ml of purified water. Add linseed
oil and 2.5g of ethanolu to 96%. Close the mixture in a short-neck bottle, shake it until
complete clarification or a thickening of the fluid is achieved. Add the rest of water and
lavender essential oil solution to the ethanol
Storage conditions: The product should be stored in well sealed bottles that are protected from
light.
28 1.4
Syrups
Syrups are concentrated solutions of sugars or polyhydric alcohols in water, in extracts of
herbal drugs or in fruit juices and are intended for internal use. From the sugars the sucrose or
glucose, fructose and invert sugar are used. From polyhydric alcohols - polyols (mannitol,
sorbitol) are used. According to Pharmacopeia, the syrups are drug forms with viscous
consistency, a sweet taste, and contains water.
Excipients
Sweetness is achieved by the use of sucrose (at least 45 % of total weight), polyols,
polyhydric alcohols or artificial sweeteners. Syrups are usually used for masking taste, but
may have a therapeutic effect if they contain drugs or are prepared by dissolving the sugars in
extracts of herbal drugs. With the exception of simple syrup, they usually contain a number of
auxiliary substances (e. g. antimicrobial substances, flavors, fragrances and dyes).
General methods of syrups preparation
1. By dissolving sucrose or sugar alcohol at an higher or room temperature:
•
in water
•
in aqueous solutions of active ingredients and excipients
•
in extracts of herbal drugs
2. Adding (dissolving) drugs, tinctures, extracts, etc. to the simple syrup.
Ad 1. Most syrups are prepared at elevated temperatures using a uniform procedure,
which can be divided into several steps:
•
Sucrose and water/liquids are weighed: the ratio of these components is in most
Pharmacopoeias 64:36
•
The sucrose is dissolved by stirring while heating (usually up to 80°C) over the
water bath or the sucrose is placed into a pre-heated liquid where it is dissolved
without heating
•
Welding solution and defoaming: after the dissolution of sucrose, the syrup,
without stirring, is quickly cooked. Do not cook unless sucrose is completely
29 dissolved. The foam that forms containing coagulated proteins or ballast
substances is collected and removed.
•
Adjustment to the prescribed density: the evaporated liquid is replenished to
the prescribed quantity by freshly boiled water.
•
Filtration and rippling - hot syrups are filtered with a suitable filter. If there are
non-filterable and sedimenting particles present, then rippling may be used
•
Filling – the still hot syrup is poured into sterilized bottles up to the neck. After
cooling, the condensed vapor is admixed with the syrup while it is being
shaken.
 Ad 2. Preparation at room temperature takes place simply by dissolving sucrose in
water or other liquids with frequent stirring or shaking. An alternate method would be to fill a
percolator with sucrose and dissolve it at a slow rate with solvent.
Packaging
Syrups are stored in glass bottles under cool conditions (8-15°C), which prevent the
microorganisms from multiplying. For the same reason, various syrups are preserved by the
addition of antimicrobial preservatives (parabens, sodium benzoate, sorbic acid, etc.).
Selected pharmacopoeial syrups: Syrupus altheae, Syrupus plantaginis, Syrupus simplex.
EXAMPLES
 Exercise 1.4.1
Syrupus simplex
Saccharosum
Aqua purificata
64.0
36.0
Preparation procedure: Sucrose is stirred into and dissolved in purified water heated to about
80°C and then is briefly cooked. The foam is removed and hot freshly boiled purified water is
added to the syrup to get 100g. If necessary, the still hot solution is filtered through a suitable
filter and filled to dry (and if necessary sterilized) containers up to the neck. Containers must
be immediately closed. The syrup is stored in a completely filled container, protected from
light, at temperature of 8°C to 15°C.
30  Exercise 1.4.2
Syrupus altheae
Altheae radix
Ethanolum 96%
Aqua purificata
Saccharosum
Methylparabenum
2.5
2.0
40.0
64.0
0.15
Preparation procedure: Radix altheae is washed with purified water at room temperature and
then placed into a glass, porcelain or enamel container. A mixture of 1g of ethanol 96% (V/V)
and 40g of purified water is then added. Stirr occasionally, and let it macerate for 2 hours at
room temperature. The extract is then filtered through a suitable filter. The drug must not be
pushed or pressed. The drug is only washed with purified water, until the required weight of
36g is achieved. Then 1g of ethanolic solution of methyl paraben is added. Sucrose is added
and the next procedure is the same as the preparation of syrupus simplex. Syrup is stored in a
completely filled container, protected from light, at a temperature of 8°C to 15°C.
 Exercise 1.4.3
Syrupus plantaginis
Plantaginis folium
Agua purificat
Saccharosum
Methylparabenum
Ethanolum 96%
5.0
45.0
64.0
0.15
1.0
Preparation procedure: Foilum plantaginis is placed into a glass or porcelain vessel, and
boiling purified water is poured over it. The vessel is tightly sealed and left to stand for 2
hours with occasional stirring. After this, the obtained liquid is filtered through a suitable
filter. The drug is then immediately pressed and the obtained extract is also filtered. These
two filtrates are then mixed, and the pressed drug is washed by purified water. This mixture of
filtrates is then refilled using this water to achieve the required weight of 36g, then 1g of
ethanol solution of methyl paraben is added. Sucrose is added and the next procedure is the
same as for the preparation of syrupus simplex. The syrup is then stored in a completely filled
container, protected from light, at a temperature from 8°C to 15°C.
31 1.5
Aromatic waters
Aromatic waters are saturated aqueous solutions of easily volatile substances, such as
essential oils. They are used mostly as taste or smell maskers, but some may also have a
moderate therapeutic effect (e.g. Aqua carminativa). For preparation, explanation of
properties and interpretation of some incompatibilities, it is important to emphasize that
aromatic waters are saturated water solutions. Because they are therefore sensitive to
temperature, they have to be kept at a temperature than during their preparation because it
would otherwise become cloudy.
The aromatic waters were originally prepared by distilling fresh or dried plant drugs with hotwater steam. This preparation is now considered to be old-fashion. The basic method remains
the preparation of dissolving oils or other easily volatile substances in water.
Excipients
Various auxiliary substances (alcohol, talc) are added for the facilitation of the preparation
and for quality improvement. Even so, the classic preparation of aromatic waters is quite
lengthy: a mixture of essential oils, ethanol and water must be intensively shaken for a long
period of time in order to achieve a saturated state.
General method of preparation
Aromatic waters may be also prepared from essential oils. In this way, these oils may be
solubilized with hydrophilic surfactants (e. g. polysorbate 80). The advantage is the speed of
preparation; the drawback is the taste and odor of polysorbate, which can often distort the
qualitative features of the product.
The general formula for the preparation of aromatic waters:
Etheroleum
Ethanolum 96%
Aqua purificata
Talcum
0.1
1.0
98.9
0.5
Note: The amount of essential oil and ethanol may vary according to the type of prescription.
Essential oils are dissolved in ethanol 96%. Purified water is added to this solution while
under a constant strong shaking and then is shaken for another 15 min. About 2g of this
32 solution is thoroughly mixed with 0.5g of talc and added back to the main portion of the
liquid. After an intensive mixing the solution is left to stand, and is then passed through a
filter moistened with purified water.
Aromatic waters have limited stability; they are easily attacked by microbes, and therefore
should be prepared only when needed. In the pharmacy it is beneficial to prepare concentrated
aromatic water in advance. Concentrated aromatic water is a 40-50% ethanolic solution of
etheroleum. This concentration is achieved by the dilution of a concentrated ethanolic solution
of etheroleum and water.
Terpenic hydrocarbons without odor are eliminated in the form of turbidity, which is removed
by filtration using talc as a sorbent. A higher proportion of ethanol has a stabilizing role - it
protects the product against microbial attack. The desired aromatic water is prepared from the
stock solution by diluting purified water at a ratio of 2 : 98 when needed.
Selected aromatic pharmacopoeial waters: Aqua carminative, Aqua carminativa rubra,
Spiritus anisi compositus (this is basically the concentrated form of aromatic water).
EXAMPLES
Representative’s pharmacopoeial aromatic plants
 Exercise 1.5.1
Aqua carminativa
Carvi etheroleum citri etheroleum
Citri oleum
Citronellae etheroleum
Coriandri etheroleum
Foeniculi etheroleum
Menthae piperitae etheroleum
Ethanolum 96%
Talcum
Aqua purificata
0.01
0.01
0.01
0.01
0.01
0.24 (12 drops)
0.50
0.50
ad 100.00
Preparation procedure: Preparation should be according to the general procedure for aromatic
water (see above), e.g., stored in a completely filled container and protected from light.
33  Exercise 1.5.2
Anisi spiritus compositus
Anisi eteroleum
Ammonii chloridum
Ethanolum 96%
Aqua purificata
2.0
3.0
40.0
55.0
Preparation procedure: Eteroleum anisi is dissolved in ethanol 96% with constant shaking;
then purified water and ammonium chloride are added. If the liquid is turbid, add 3g talc,
shake, and leave it to stand for a few hours with occasional stirring and then filter it. Store
where it will be protected from light.
Further examples of aromatic waters
 Exercise 1.5.3
Aqua mentehae piperitae
Menthae piperitae etheroleum
Ethanolum 96%
Aqua purificata
Talcum
0.1
1.0
98.9
0.5
Preparation procedure: It is prepared according to procedure for aromatic waters.
 Exercise 1.5.4
Aqua mentehae concentratae
Menthae piperitae etheroleum
Ethanolum 96%
Aqua purificata
Talcum
1.8
q.s.
58.2
3.0
Preparation procedure: Menthae piperitae etheroleum is dissolved in 40g of ethanol 96%, and
under constant shaking is diluted with purified water. Shake for 15 minutes and leave to stand
for 24 hours at room temperature. Then mix about 10g of this mixture with 3g of talc, shake
thoroughly, and add it back to the main portion of the liquid. After shaking, this mixture is left
to settle and then passed through a dry filter. To this filtrate is added 2 % of ethanol 96%. This
34 addition of ethanol prevents the formation of turbidity in case the temperature falls during
storage.
35 1.6
Mucilages
Mucilages are formed from swelling expanding polymeric substances. They can be natural,
semisynthetic or synthetic. Viscous colloidal solutions or dispersions are created by the
swelling of these substances in water (or different hydrophilic solvents).
Excipients
Substances which allow the creation of mucilage are usually able to transform themselves
from a "sol" to a "gel" form. The transformation from "sol" to "gel" is performed with higher
concentrations of polymeric substances during changes of temperature, a change of pH, or
from being in the presence of certain ions. These substances are often considered to be "gelcreating".
It is not always easy to say whether a product belongs to a group of mucilages or gels. From a
theoretical point of view, mucilage is the colloidal system in a state of "sol". From a practical
point of view the mucilage is considered to be a polymeric solution (dispersion) having the
characteristics of a viscous liquid.
Method of preparation
The preparation of gels and mucilages is not uniform, since different substances require
different conditions for swelling, dissolution and/or gelation (sol-gel transition). It is generally
prepared by placing a uniform, finelyp-ulverized gelling agent on the surface of a liquid,
usually at room temperature. The premix of the gelling agents with alcohol or glycerol is
sometimes recommended for substances that form clumps easily, or for substances having
trouble with expansion.
Processes of swelling
1. Spontaneous swelling at room temperature (Accacia, MC).
2. Swelling at higher temperature (CMC, agar).
3. Swelling at room temperature, followed by heating Gelatine, starch.
4. Dispersal at higher temperature, followed by swelling during cooling
HPMC, starch.
5. Neutralization of swollen dispersion (Carbomers).
36 EXAMPLES
Selected Pharmacopoeial mucilages
 Exercise 1.6.1
Mucilago accaciae
Accaciae gummi dispersion desiccatum
(Accaciae gummi)
Aqua conservans
10.0
ad 30.0
Preparation procedure: Pulverized arabic gum is dissolved in Aqua conservans. If necessary,
it is filtered and bottled. It is stored in containers protected from light, at a temperature
ranging from 8°C to 15°C.
 Exercise 1.6.2
Mucilago methylcellulosi
Methylcellulosum
Glycerolum 85%
Aqua purificata
2.5
10.0
ad 100.0
Preparation procedure: Methyl cellulose is dispersed in about 40ml of purified water and left
to stand for 15 minutes. The expanded mixture is stirred until smooth. The rest of the
remaining mixture of glycerol and purified water is then added and stirred into the transparent
slime. It is stored in containers protected from light, at a temperature ranging from 8°C to
15°C.
37 Other mucilages
 Exercise 1.6.3
Carmellosi natrici mucilago
Carmellosum sodium
Glycerolum 85%
Aqua conservans
2.0
10.0
ad 100.0
Preparation procedure: A mixture of Aq. conservans and glycerol is heated to approximately
85°C; while constantly stirring, sodium carmellose is added. After dissolving, evaporated
water is added. The mixture is then stirred further.
 Exercise 1.6.4
Mucilago methylcellulosi
Methyl cellulosum
Aqua purificata
1.0
ad 100.0
Preparation procedure: Approximately the half the amount of purified water is heated to 80°C
and is poured into a melamine mortar blender. Methyl cellulose is spread on the water surface
and left to swell for 15 minutes. The rest of the water is cooled to a temperature of about 0°C.
Cold water or ice drift is put into the swollen methyl cellulose and stirred into the
homogenous, transparent mucilage.
Note: In addition to the above mentioned or pharmacopoeial procedure (see above, Exercise
1.6.2), methyl cellulose mucilage can be prepared by another simple, but lengthy method. The
methyl cellulose is left to swell at room temperature for at least 12 hours, but usually for
overnight.
38 1.7
Herbal drug preparations
Products obtained by extraction methods are primarily fluid extracts from plants. There are
infusions, decoctions, tinctures and extracts that are traditional pharmacopoeial and
pharmaceutical forms.
Active ingredients
They contain a mixture of active, side and ballast substances. The extracts are composed of
the substances with different physical and chemical properties, varying stability and solubility
and therapeutic values.
Therefore, some types of extracts, like stable dried extract, are preferred more in recent years.
Dried extracts ensure a stable content of active substances, mixtures without admixtures, or
they contain purified active pharmaceutical ingredients.
Extractive methods are divided according to their course: they can be periodic, semi-continual
and continual.
Methods of preparation
1. Periodic extraction methods - maceration. Ingredients are extracted from drugs to
a solvent in a closed system. This means that the drug and the solvent is placed
together in a container. After a certain period of time, the extract and the residual
plant remains. Maceration can take place under different temperatures, in one step
or in several, and with a different velocity of movement between solvent and drug.
Maceration is used for the preparation of infusions, decoctions, tinctures an
extracts.
2. Semi-continuous extraction methods - percolations. Drug is loaded into a
container and the in-flow and out-flow of the solvent are continuous. Percolations
take place at room temperature, either in one or in the series of percolators.
Percolation is used for the preparation of tinctures an extracts.
3. Continuous
extraction
methods.
Continuous
extraction
methods
are
characterized by utilizing a continuous supply of drug and fluid with a continuous
separation of solvent and residual of drugs. These methods require special
production equipment used in pharmaceutical production.
39 General requiremets in the preparation of extracts (infusions, decoctions, tinctures, extracts)
from herbal drugs and methods of extractions:
 Unless otherwise prescribed, the following parts of flowers are used for preparation:
finely cut and very finely cut flowers, leaves, pulps, stems and roots, and coarsely
powdered fruits and seeds.
 If the amount of drug is not prescribed, the preparation of the infusions is performed in
ratio: for 10g of drug 100g extract is prepared. In the case of mucilage drugs, for 10g
of the drug, 200g of extract is prepared.
 For the preparation of tinctures of potent and highly potent drugs, 10g of the drug is
used for the preparation of 100g of tincture. In other cases, 20g of drug is used for the
preparation of 100g of tincture.
 Suitable adjuvants increasing extraction methods and stabilizing agents can be used
according to the nature of the drug.
 For drugs containing alkaloids, an acidifying agent such as citric acid is added.
According to the quantitative content of alkaloids it is used in the form of a prewetting mixture; e.g., for 1g of radix with a content of 0.02g of alcaloids, 0.02g of
citric acid is used. The extraction of saponine and mucilage drugs is better performed
in a slightly alkaline environment. Prescribed drugs are added to the finished extract.
These are aqueous extracts, which are usually prepared at the time needed (ex tempore).
Maceration methods take place at room temperature or higher, by dissolving dried extracts,
and by diluting concentrated extracts.
Methods of preparation
1. Preparation at room temperature
Infusions of drugs containing a mucilage substance: The drug is macerated with water at room
temperature for 30 minutes, and stirred occasionally. The mucilage, obtained without
pressing, is filtered, and the filter is washed with an adequate amount of the solvent so that the
prescribed quantity of the product can be received.
40 2. Preparation at higher temperature
Extracts which are prepared at higher temperatures are called decoctions and infusions. The
drug is placed in a porcelain mortar blender and kneaded with water three to five times the
quantity, until it is evenly wetted and left to stand for 15 min. The drug is then placed into a
suitable container and capped. Depending on whether the infusion or decoction is being
prepared, proceed is follows:
 For the infusions: The drug is mixed with the remaining boiling water, placed over a
boiling water bath for 5 minutes, stirring occasionally. The container is kept for 45
minutes at room temperature while occasionally being stirred. The extract is filtered,
pressed out, and then the container is refilled up to the required quantity of product
with water, which was used for washing the filter.
 For the decoctions: The drug is mixed with the remaining boiling water, placed over
a boiling water bath for 30 minutes, stirring occasionally. The extract is filtered while
still hot, pressed out and the container is refilled up to the required quantity with
water, which was used for washing the filter.
3. Maceroinfusion
Extraction is initially taken place at room temperature and then at a temperature continually
decreasing from 60-70°C down to room temperature: The drug is then put in with half of the
amount of solvent, mixed, and left to infuse for 15 minutes. The other half of the boiling
solvent is then added to the mixture, and left to stand for 15 minutes.
41 EXAMPLES
Preparation at room temperature
 Exercise 1.7.1
Rp.
Althaeae radicis infusi
5.0 : 100.0
D.S. 3 x1 spoonful
 Exercise 1.7.2
Rp.
Lini seminis infusion
5.0 : 100.0
D.S. 1 spoonful several times a day
Preparation at higher temperatures
 Exercise 1.7.3
Rp.
Quercus corticis decocti
5.0 : 100.0
D.S. Poultice

Exercise1.7.4
Rp.
Uveae ursi foil decocti
5.0 : 100.0
D.S. small spoonful 2-3 x per day

Exercise 1. 7.5
Rp.
Tiliae floris infusi
5.0 : 100.0
D.S. 2 spoonfuls 3 x per day
42  Exercise 1. 7.6
Rp.
Crataegi folii cum flore infusi
4.5 : 100.0
D.S. 2 spoonfuls 2-3 x per day
 Exercise 1. 7.7
Rp.
Milefolii herbae infusi
5.0 : 100.0
D.S. 2 spoonfuls 2-3 x per day
The extraction of saponine compounds should be performed in a slightly alkaline medium,
which is reached by adding 0.1g of sodium carbonate or hydrogencarbonate or by adding 0.5g
of 10% ammonia solution to the 1.0g of drug. These substances are added to solvent, which is
dedicated to the pre-wetting of the drug.
 Exercise 1.7.8
Rp.
Verbasci floris infusi
1.5 : 100.0
D.S. Drink during the day
 Exercise 1.7.9
Rp.
Betulae folii infusi
5.0 : 100.0
D.S. Use 1 spoonful 3-4 x per day
Tinctures are usually alcoholic extracts from drugs or the ethanol solutions of dry extracts.
They are prepared by maceration at room temperature, the dissolution of the dry extracts, and
by percolation and stirring the extraction.
43 General methods of preparation
1. Maceration: The prescribed amount of drug is poured into a suitable vessel, along with the
prescribed amount of solvent. The vessel is closed and left to stand for 7 days and is stirred
occasionally. The obtained liquor is decanted and the drug is pressed out. Both liquors are
mixed and replenished with solvent which was used for washing the drug previously. Then
the liquor is left to stand in a dark, cool place for at least 12 hours to become transparent.
Then the transparent liquor is decanted, while the drug on the filter is washed with an
adequate amount of solvent so that the prescribed quantity of the tincture can be received.
2. Dissolution: The prescribed amount of the solvent is added to the prescribed amount of
dried extract. The vessel is closed and left to stand in a dark place and stirred occasionally
until it is dissolved. The liquid is then left to stand once more in a dark, cool place for at least
12 hours until it becomes transparent. Then the transparent liquor is decanted. The filter is
washed with an adequate amount of the solvent so that the prescribed quantity of the tincture
can be received.
3. Percolation: The drug is wetted with the prescribed quantity of solvent and left to stand for
about 6 hours. Then the drug is transferred to a percolator along with an appropriate quantity
of solvent so that the drug could be immersed. The percolator is closed and left to stand for 24
hours. The liquor flows out through the half-open cock and solvent is added continually. Flow
velocity is about 1/50 of percolator volume per hour. When 1/2 of the prescribed volume of
the tincture is obtained, the percolation is stopped. Then the rest of liquor contained in the
drug is left to drip out. The drug is then removed, pressed out and both liquors are mixed and
refilled to the prescribed weight.
Extracts are concentrated liquids, either dried or semi-solid, prepared by percolation or
maceration using alcohol or other suitable solvents.
Method of preparation
 The ratio of dried drugs to solvent and liquid extracts is usually 1 : 1.
 Semi-solid and dried extracts are usually transformed to the desired consistency by the
evaporation of the solvent under reduced pressure and/or a reduced temperature, if
necessary.
44  Standardized extracts are adjusted to the defined content of the substance by using
suitable inert substances such as lactose or dextrin.
Selected pharmacopoeial tinctures: Arnicae tinctura,
Aurantii amari pericarpi tinctura,
Beladonnae folii tincture, Cinnamomi tincture, Gallarum tincture, Gentianae tincture,
Ipecacuanhae tincture normata, Myrrhae tincture, Tinctura amara, Tormantiallae tincture,
Valerianae tinctura
Selected pharmacopoeial fluid extracts: Matricariae extractum fluidum, Plantaginis extractum
fluidum.
45 1.8
Eye drops
Eye drops are sterile, aqueous or oily solutions, emulsions or suspensions of one or more
active substances intended for insertion into the eye.
Ensuring the sterility of eye drops
 Preparation in suitable environmental conditions (grade A, in the case that then
follows sterilization in an autoclave - grade C)
 Using sterile or microbiologically safe drugs and other excipients (sterile water as
solvent).
 Sterilization of the preparation (membrane filtration – pharmaceutical practice).
 Suitable containers – glass or plastic eye-dropper bottle (sterile with integrated
dropper, secure, airtight).
Requirements and excipients
 Clarity – eye drops examined under suitable conditions of visibility, are practically
clear and practically free from particles.
 Tonicity – lacrimal fluid is isotonic to the blood. Eye drops are considered to be
isotonic when its tonicity is equal to 0.9% of the sodium chloride solution. Hypotonic
eye drops must be adjusted for isotonicity by the addition of sodium chloride, sodium
nitrate (for drugs based on Ag+ ions), glucose, mannitol and others. Hypertonic eye
drops are not adjusted.
 pH – buffers (phosphate, borate, acetate) are used to minimize pH change during
shelf life because this could affect a drug’s solubility, stability and consequently, its
bioavailability.
 Sterility – eye drops must be sterile. Sterility is achieved through membrane filtration
(pore size less than 0.22 µm) into a sterile container. Other methods include dry heat,
autoclaving (steam under pressure) or gas sterilization with ethylene oxide.
Ophthalmic solutions are generally packaged in multi-dose containers. Since there is
the possibility of inadvertent bacterial contamination of the contents with repeated
patient use, a preservative must be added. Preservatives should be safe in regard to
46 patient sensitivity and should be compatible with the other ingredients in the
formulation.
 Preservatives (usually quaternary ammonium compounds or organic mercurials) that
are commonly used in ophthalmic preparations are listed in Table 1. Eye drops can not
contain a antimicrobial preservative, if the doctor requires so (sine antimicrobico!). In
this case the eye drops are intended for one use only. Eye drops intended for use in
surgical procedures do not contain antimicrobial preservatives; they are dispensed
from single-dose containers.
 The particle size of ophthalmic suspensions must be kept to a minimum to prevent
irritation of the eye and must fall within the pharmacopoeia limit. It is recommended
that the particles should be less than 10µm in size to minimize eye irritation. The
micronized form of the drug can be used to meet this requirement.
 Volume of eye drops should not be bigger than 10ml if it is not prescribed or
approved otherwise.
Labels: Red labels
 Expiration date - usually 1 month; longer shelf life of preparations has to be approved
by the State Institute for Drug Control
 Regime of application
 Storage conditions
 Only for external use
 Date of preparation
 Address of pharmacy
 Pharmacist´s signature
Important abbreviations:
o O.d. - right eye
o O.s. - left eye
o O.e. - each eye
o O.b.- both eyes
47 o ODS - both eyes
Labeling for multi-dose preparations
o Interval after initial opening for use of eye drops - 4 weeks (during shelf life).
o Added antimicrobial preservative – cum antibicrobico (c.a.).
Labeling for single-dose preparations
o Contains amount of eye drops intended for total or partial use on 1 occasion
only!!!
o Preservatives are not permitted - sine antimicrobico (s.a.)
o For one application only after opening (immediately)
48 Table 1. Compatibility of preservatives with drugs
BenzalkoCarbethopenNium chloride deciniumbro0.01%
mide 0.02%
DRUG
Phenylmercuric Thiomersal
borate (nitrate,
0.002 acetate)
0.01%
0.001-0.002%




Acidum boricum
Argenti nitras
Argenti
diacetyltannas
albuminatus
Atropini sulfas
monohydricus
Calcii chloridum
Ethylmorphini
hydrochloridum
dihydricum
Epinephrini
tartras












 





 




Fluoresceinum
natricum
Homatropini
hydrobromidum
Kalii iodidum
Natrii iodidum
Natri tetraboras
decahydricus



Physostigmini
salicylas
Pilocarpini
hydrochloridum
Procaini
hydrochloridum
Resorcinolum
Scopolamini
hydrobromidum
trihydricum
Tetracaini
hydrochloridum
Zinci sulfas
heptahydricus
Note:
 










 



 



























 - suitable
 - unsuitable
 - contradictory information
49 Note
Suitable for
single-dose
preparation



 - recommended
Chlorhexidindiacetate
0,01%



Table 2. Preservatives for eye preparations
GROUP
Quarternary ammonium
compounds
Range of used
concentration (%)
Recommended
concentration (%)
0.004 – 0.02
Benzalkonium chloride
0.01 – 0.02
Benzethonium chloride
0.01 – 0.02
Cetrimide
0.02 -0.3
0.001- 0.04
new,
limited usage
6-8
Phenylmercuric nitrate
0.002
Phenylmercuric acetate
0.001 – 0.004
0.002 – 0.02
0.002 – 0.01
0.5 – 0.9
4-6
Chlorbutanol
0.5
Benzyl alcohol
0.5
0.25 – 0.5
Fenylethyl alcohol
Esters of p-hydroxybenzoic acid
(parabenes)
usually in combination
with EDTA
0.02
0.001 – 0.004
Aromatic and alifatic alkohols
activity is higher at
neutral and basic pH
0.02
Phenylmercuric borate
Thiomersal
4 - 10
0.01 – 0.1
Carbethopendecinium bromide
Organic mercurials
Note
0.01
Cetylpyridinium chloride
Polyquaternium-1 (polyquat)
Range of pH for
optimal activity
max. 0.1
methylparabene
0.015 – 0.05
propylparabene
0.005 – 0.01
4-8
Others
chlorhexidine
0.01 – 0.05
0.01
50 6-8
Used rarely in
combination with other
preservatives; low
efficiency, irritability
EXAMPLES
 Exercise 1.8.1
Acidi borici oculoguttae – Eye drops with boric acid – in pharmacopoeia;
Synonymum. Collyrium acidi borici
Acidum boricum
Thiomersalum
Aqua purificata (sterilisata)
ad
0.169
0.0002
……..10.0
Preparation procedure: Dissolve 0.0002g of thiomersal (preservative, use 0.1% solution) in
9g sterile water warmed to 60-70 °C. Dissolve boric acid (API) in this solution. After cooling,
add evaporated water to 10.0 g. Sterilize by membrane filtration (0.22 µm) and fill into the
suitable container in environment of grade A. It is possible also to sterilize it in final
container by autoclaving (15 minutes, 121 ºC).
Phenylmercuric borate (0.01g/l) is another suitable preservative.
Storage conditions: Keep out of light!
Notes: It is usually dispensed from a 10ml container
If the doctor prescribed Solutio acidi borici or Acidum boricum solutum, and from the
prescription it is obvious that the preparation is intended for eye administration, Acidi borici
oculoguttae is dispensed.
 Exercise 1.8.2
Chloramphenicoli oculoguttae – Eye drops with chloramphenicol – in pharmacopoeia
Synonymum. Collyrium chloramphenicoli
Chloramphenicolum (250)
Acidum boricum
Natrii tetraboras decahydricus
Thiomersalum
Aqua purificata (sterilisata)
ad
0.05
0.15
0.03
0.0002
10.0
Preparation procedure: Dissolve sodium tetraborate, boric acid and thiomersal (preservative,
use 0.1% solution) by warming in approximately 9g of sterile water. When the temperature
descreases to approx. 70C, add powdered chloramphenicol (250µm), mix the solution at the
51 same temperature until all chloramphenicol is dissolved. After cooling, add evaporated water
to 10.0g. Sterilize by membrane filtration (0.22µm) and pour it into a suitable container in a
grade A environment.
Phenylmercuric borate (0.02g/l) is another suitable preservative.
Storage conditions: Keep away from light!
Notes: It is usually dispensed from a 10ml container. It cannot be dispensed without a
prescription.
 Exercise 1.8.3
Fluoresceini natrici oculoguttae 2.5% – Eye drops with sodium fluorescein – in
Pharmacopoeia
Fluoresceinum natricum
Natrii chloridum
Thiomersalum
Aqua purificata (sterilisata)
Preparation procedure:
ad
0.25
0.20
0.0002
10.0
First, dissolve thiomersal (preservative, use 0.1% solution) and
sodium salt of flourescein and sodium chloride. Add evaporated water to 10.0g. Sterilize by
membrane filtration (0.22µm) and pour into a suitable container in a grade A environment.
Storage conditions: Keep out of light!
Notes: It is usually dispensed from a 10ml container
 Exercise 1.8.4
Kalii iodidi oculoguttae – Eye drops with potassium iodide – in pharmacopoeia;
Synonymum. Collyrium kalii iodati
Kalii iodidum
Natrii chloridum
Natrii thiosulfas pentahydricus
Thiomersalum
Aqua purificata (sterilisata)
ad
0.20
0.02
0.002
0.0002
10.0
Preparation procedure: First, dissolve thiomersal (preservative, use 0.1% solution) in 9g of
sterile water, then sodium thiosulphate pentahydrate, potassium iodide and sodium chloride.
52 Add evaporated water to 10.0g. Sterilize by membrane filtration (0.22µm) and pour it into a
suitable container in a grade A environment.
Storage conditions: Keep out of light!
Notes: It is usually dispensed from a 10ml container
 Exercise 1.8.5
Natrii tetraboratis oculoguttae cum acido borico - Eye drops with sodium tetraborate
and boric acid – in pharmacopoeia;
Synonymum. Natrii teraboratis oculoguttae, collyrium boraxatum
Acidum boricum
Natrii tetraboras decahydricus
Thiomersalum
Aqua purificata (sterilisata)
0.175g
0.025g
0.0002g
ad 10.0g
Preparation procedure: Dissolve 0.0002g of thiomersal (preservative, use 0.1% solution) in
9g of sterile water warmed to 60-70°C. Dissolve boric acid and sodium tetraborate
decahydrate into this solution. After cooling, add evaporated water to 10.0g. Sterilize by
membrane filtration (0.22µm) and pour into a suitable container in a grade A environment. It
is also possible to sterilize the eye drops in the final container by autoclave (20 minutes,
121ºC).
Storage conditions: Keep out of light!
Notes: It is usually dispensed from a 10ml container
 Exercise 1.8.6
Pilocarpini hydrochloridi oculoguttae – Eye drops with pilocarpine hydrochloride – in
pharmacopoeia; Synonymum. Pilocarpini oculoguttae, collyrium pilocarpinii chlorati
Pilocarpini hydrochloridum
0.1
Carbaethopendecinii bromidum
0.002
Acidum boricum
0.127
Natrii tetraboras decahydricus
0.003
Aqua purificata (sterilisata) ad….10.0
ad
0.2
0.002
0.85
0.002
10.0
Preparation procedure: Dissolve boric acid (API) and sodium tetraborate decahydrate (API)
in sterile water (carbon dioxide-free) warmed to 60-70°C. After cooling, add pilocarpine
53 hydrochloride and carbethopendecinium (preservative, use 0.5% solution) bromide. Add
evaporated water to 10.0g. Sterilize by membrane filtration (0.22µm) and pour into a suitable
container in a grade A environment.
Storage conditions: Keep out of light!
Notes: It is usually dispensed from a 10ml container
Exercise 1.8.7
Zinci sulfatis oculoguttae – Eye drops with zinc sulphate - in pharmacopoeia;
Synonymum. Collyrium zinci sulfurici
Zinci sulfas heptahydricus
Acidum boricum
Natrii tetraboras decahydricus
Thiomersalum
Aqua purificata
ad
0.025
0.162
0.003
0.0002
10.0
Preparation procedure: Dissolve 0.0002 g of thiomersal (preservative, use 0.1% solution) in
9g sterile water warmed to 60-70°C. Dissolve boric acid and sodium tetraborate decahydrate
into this solution. After cooling, dissolve zinc sulphate decahydrate. Add evaporated water to
10.0g. Sterilize by membrane filtration (0.22µm) and pour into suitable container in a grade
A environment. It is also possible to sterilize the eye drops in the final container by autoclave
(15 minutes, 121ºC).
Storage conditions: Keep out of light!
Notes: It is usually dispensed in a 10ml container
 Exercise 1.8.8
Rp.
Argenti nitratis oculoguttae
1% - 10.0
D.S. For application into the eyes of newborns after birth
Sine antimicrobico! Suo nomine. Pro ordinatione.
Note: Sine antimicrobico! – Without preservative!
Suo nomine. - Write name of preparation on the label. Pro ordinatione. – Intended for
medical office.
54  Exercise 1.8.9
Rp.
Sol. Atropini sulfatis 0.5%
10.0
D.S. Eye drops. 1 drop twice a day into conjuctival sac. Sub signo
veneni!
Notes: Sub signo veneni! – Mark as poison!
 Exercise 1.8.10
Rp.
Tetracaini chloride
Aq. sterilisatae
0.025
ad 10.0
M.f. collyr.
D.S. Cum formula, pro ordinatione. Sine antimicrobico!
Notes: Cum formula – Write the composition on the label
 Exercise 1.8.11
Rp.
Ethylmorphini hydrochloride
Aq. sterilisatae
0.05
ad 10.0
M.f. collyr.
D.S. Eye drops. 1 drop twice a day into conjuctival sac.
 Exercise 1.8.11
Rp.
Physostigmini salicylatis
Aq. sterilisatae
0.01
ad 10.0
M.f. collyr.
D.S. Eye drops. 1 drop four times a day into conjuctival sac.
55  Exercise 1.8.12
Rp.
Homatropini hydrobromidi
Aq. sterilisatae
0.1
ad 10.0
M.f. collyr.
D.S. Eye drops. Suo nomine. Pro ordinatione. Sub signo veneni!
 Exercise 1.8.13
Rp.
Scopolamini hydrobromidi
Aq. sterilisatae
0.01
ad 10.0
M.f. collyr. D.S. Eye drops. 1 drop four times a day into conjuctival sac.
Sub signo veneni!
56 1.9
Eye lotions
Eye lotions are sterile, aqueous solutions intended for rinsing or bathing the eye, or for
impregnating eye dressings. The maximum volume of multi-dose eye lotions is 200 ml.
Excipients
 Sterile water.
 Excipients for adjustment of osmotic pressure.
 Viscosity increasing agents.
 Excipients for the adjustment and stabilization of pH.
 Preservatives.
Eye lotions without preservatives that are prescribed by a doctor, are dispensed in single-dose
containers. Eye lotions intended for open wounds, or for surgery, are not allowed to contain
preservatives and are put into single-dose containers. Per visual examination, eye lotions
should be clear and without particles.
EXAMPLES
 Exercise 1.9.1
Acidi borici aqua ophtalmica – Eye lotion with boric acid
Acidum boricum
Thiomersalum
Aqua purificata
1.690 g
0.002 g
ad 100.0 g
Preparation procedure: Dissolve 0.0002g of thiomersal (preservative) in 90g sterile water
warmed to 60-70°C. Dissolve boric into this solution. After cooling, add evaporated water to
100.0g. Sterilize by membrane filtration (0.22µm) and pour into a suitable container in a
grade A environment. It is possible also to sterilize it in final container by autoclaving (15
minutes, 121ºC).
Storage conditions: Keep out of light!
Notes: It is usually dispensed from a 100 ml container, maximum 200 ml. Separated
applicator must pass a sterility test.
57 1.10 Nasal drops
Nasal drops are solutions, emulsions or suspensions intended for the instillation, or spraying,
into the nasal cavities. Although nasal application is considered to be an alternative pathway
for systemic administration, most nasal drugs prepared in the pharmacy are used for their
local effect.
Nasal mucosa is partially covered with cilia epithelium and mucus, which trap and remove
dust and pathogens from the air as it flows through the nasal cavity. Therefore the
composition of nasal preparation should not adversely affect the function of the nasal mucosa
and its cilia. For this reason, hydrophilic preparations are prefered, and lipophilic diluents
such as liquid parafine and linseed oil are not permitted. Parabenes (negative effects on the
cilia) and borate buffers (toxic effects) are not suitable for nasal application.
Nasal mucosa is sensitive to hypotonic solutions, therefore aqueous nasal drops should be
isotonic (non-aqueous and lipophilic nasal drops are not adjusted). Rules for tonicity
adjustment are the same as they are in the case of eye drops.
Excipients
Viscosity-increasing agents (cellulose derivates – HEC, HPMC, MC; others - PVA, PVP)
are added to formulations to increase bioavailability by ensuring that there is longer contact
time. Nasal drops very often contain excipients for smell correction (essential oils).
Preservatives (usually quaternary ammonium compounds or organic mercurials) are added to
ensure the microbial quality of aqueous nasal drops. Carbethopendecinium bromide is
preferred because of its eutrofic effect on the nasal mucosa.
Labels: red label - information for patients, storage conditions, name of added preservative,
sterility (for preparations intended for surgical procedures)
Shelf life: maximum 1 month
Amount: 10-30g
58 EXAMPLES
 Exercise 1.10.1
Acidi borici rhinoguttae cum ephedrino – Nasal drops with boric acid and ephedrine –
in pharmacopoeia; Synonymum. Acidi borici cum ephedrino naristillae
Ephedrini hydrochloridum
Acidum boricum
Aqua purificata
ad
0.2
0.6
20.0
Preparation procedure: Dissolve boric acid in purified water warmed to 60-70°C. After
cooling, add ephedrine hydrochloride. Add evaporated water to 10.0g . Filter.
Storage conditions: Cold place (8-15°C); Keep away from light!
Notes: this cannot be dispensed without a prescription. It can be used for a maximum of 1
week.
Shelf life: 1 month
 Exercise 1.10.2
Rp.
Argenti diacetyltannatis albuminati
Aq. purificatae
Aq. menthae piperitae
0.1
aa ad 10.0
M.f. sol.
D.S. Nasal drops. Half of dropper to each nostril three times a day
Preparation procedure: Place a colloidal silver on the surface of a mixture of purified water
and peppermint aromatic water. Let it slowly hydrate. Do not forget to add an excipient for
tonicity adjustment. Mix the prepared colloidal solution. Filter through gauze.
Storage conditions: Keep out of light!
Shelf life: 3 weeks
59  Exercise 1.10.3
Rp.
Scopolamini hydrobromidi
0.02
Agari
0.04
Aq. purificatae
ad 20.0
M.f. sol
D.S. Nasal drops Ad manus medici! Cum formula. Sub signo veneni!
Preparation procedure: Do not forget to add an excipient for tonicity adjustment, as well as a
suitable preservative (use in form of a solution)! Dissolve agar (viscosifier) into a small
amount of boiled purified water. Dissolve pilocarpine hydrochloride in the rest of the water
containing the preservative and excipient for tonicity adjustment. After cooling, mix the two
solutions together.
Storage conditions: Keep out of light!
Shelf life: 1 month
 Exercise 1.10.4
Rp.
Ephedrini hydrochloride
Carbethopendecinii bromidi
Foeniculi etherolei
Sol. methylthionii chloridi 0,5%
Methylcellulosi
Sol. natrii chloridi isoton
0.1
0.01
gtt I
gtt II
0.2
ad 20.0
M.f. sol.
D.S. Nasal drops. Apply 3 times a day.
Preparation procedure: Layer methylcellulose on the surface of half amount of isotonic
solution of NaCl. Let it hydrate slowly (30 minutes). Dissolve ephedrine hydrochloride (API),
carbethopendecinium bromide (preservative) in the rest of isotonic solution of NaCl, and add
one drop of fennel oil and two drops of methylene blue. Mix the solutions together.
Storage conditions: Keep out of light!
Notes: It can be used for a maximum of 1 week.
60 Shelf life: 1 month
 Exercise 1.10.5
Rp.
Dexamethasoni
Mucilaginis methylcellulose
Aq. Purificatae
0.005
6.0
ad 20.0
M.f. suspensio.
D.S. Nasal drops. 3 drops to each nostril 5 times a day
Preparation procedure: Use the previously prepared solution of dexamethasone in propylene
glycol and a 2.5% viscous solution of methylcellulose (PC 2009). Do not forget to add a
suitable preservative (use in form of a solution)!
Storage conditions: Keep out of light!
Shelf life: 1 month
61 1.11 Ear drops
Ear drops are solutions, emulsions or suspensions suitable for application to the auditory
meatus without exerting harmful pressure on the eardrum. They may also be placed in the
auditory meatus by means of a tampon impregnated with the liquid. They are designed
especially for external ear treatment (for softening and dissolution of cerumen – ear wax,
cleaning of the external ear canal, dermatitis of the external ear canal, and infection). They are
rarely used for treatment of the innner ear.
Excipients
Unlike eye and nasal drops, ear drops are most often based on non-aqueous hydrophilic
diluents (ethanol, glycerol, propylen glycol, isopropyl alcohol, polyethylene glycols) or
lipophilic diluents (liquis paraffins, plant oils).
The outer auditory canal has a normal pH of 4 to 5, which has bacteriostatic or germicidal
effect to most microorganisms causing otitis. To adjust the pH to lower values, excipients
such as citric acid, boric acid, hydrochloric acid, sodium hydroxide, acetate, borate and
phosphate buffers are used. Preservatives and excipients for tonicity adjustment are only
added to aqueous ear drops. It is also possible to add viscosity-increasing agents.
Preparations for the application to the injured ear, particularly in such cases where the
eardrum is perforated, or prior to surgery, must be sterile, free from antimicrobial
preservatives and supplied in single-dose containers.
Package
Containers for ear drops are usually multi-dose, and made of glass or plastic with an
integrated dropper or screw cap with a dropper.
Ear drops should be heated to body temperature before application because cool ear drops can
lead to the irritation of the inner ear along with vertigo, nausea and vomiting.
Labels:
red label - information for patients, storage conditions, names of any added
preservatives, and sterility (for preparations intended for surgical procedures)
Shelf life: maximum 1 month
Amount: 10-30 g
62 EXAMPLES
 Exercise 1.11.1
Aluminii acetotartratis otoguttae – Ear drops with aluminum acetate tartare – in
pharmacopoeia; Synonymum. Instillatio aluminii acetico-tartarici
Aluminii acetotartratis solution
Aqua purificata
Ethanolum 60%
8.0
4.0
8.0
Preparation procedure: Mix solution of aluminium acetate tartrate with mixture of purified
water and ethanol 60 %.
Storage conditions: Keep out of light!
Notes: The preparation may not be used if it contains any sediment
Shelf life: 1 month
 Exercise 1.11.2
Rp.
Ac. borici
Ethacridini lactatis
Spiritus dilute
0.3
0.01
ad 10.0
M.f. sol.
D.S. Ear drops. Insert a gauze pad and drop every 2 hours.
Preparation procedure: Dissolving
Storage conditions: Keep out of light!
Notes: Flammable!
Shelf life: 1 month
63  Exercise 1.11.3
Rp.
Zinci sulfatis
Glyceroli 85%
Aq. purificatae
0.1
aa ad
20.0
M.f. sol.
D.S. Ear drops. A half dropper to the auditory meatus three times a day.
Preparation procedure: Dissolving
Storage conditions: Keep out of light!
Shelf life: 1 month
 Exercise 1.11.4
Rp.
Natrii carbonatis
0.4
Glyceroli 85%
ad
20.0
M.f. sol.
D.S. Ear drops. A half dropper to the auditory meatus three times a day.
and cover with wet gauze.
Preparation procedure: Dissolve sodium carbonate in glycerol in a close-neck bottle by
warming over the water bath.
Storage conditions: Keep out of light!
Shelf life: 1 month
64  Exercise 1.11.5.
Rp.
Ac. salicylici
Ureae purae
Aq. Purificatae
Spiritus dilute
0.02
1.0
8.0
ad 20.0
M.f. sol.
D.S. Ear drops. A half dropper to the auditory meatus three to five times
a day.
Preparation procedure: Dissolving
Storage conditions: Keep out of light!
Shelf life: 1 month
65 1.12 Emulsions
Emulsions are a two-phase system in which one liquid is dispersed throughout another liquid
in the form of small droplets. Polar liquid is called the water phase (water, aqueous solution)
and non-polar liquids are the oil phase (hydrocarbons, oils, higher alcohols, wax, etc.).Where
oil is the dispersed phase and an aqueous solution is the continuous phase, the system is
designated as an oil-in-water emulsion. Conversely, where water or an aqueous solution is the
dispersed phase and oil or oleaginous material is the continuous phase, the system is
designated as a water-in-oil emulsion.
Excipients
Emulsions are stabilized by emulsifying agents that prevent coalescence - the merging of
small droplets into larger droplets - and, ultimately, into a single separated phase. There are
three types of emulsifiers:
1. Surface-active agents – surfactants (reduce the surface tension at the
interface between oil and water molecules - adsorbant on the surface layer)
2. Macromolecular materials (primarily increase the viscosity of the external
phase (some are surface-active)
3. Finely divided solids (absorb on the interface and create a film of insoluble
particles around the dispersed droplets)
Emulsifying agents (surfactants) accomplish this by concentrating in the interface between the
droplet and the external phase, and by providing a physical barrier around the particle for
coalescence. Surfactants also reduce the interfacial tension between the phases, thus
increasing the ease of emulsification upon mixing.
Emulsions are intended for both internal and external use. Some emulsions intended for
topical application to the skin are known as liniments (Linimenta) and lotions (Lotiones).
Other preparations that have the characteristics of an emulsion should be designated
"emulsion" (e.g. ointments, suppositories).
General methods of solution preparation
Emulsions are prepared by a procedure suitable for the type and composition of the emulsion.
Generally, the temperature of both phases should be the same. The drug can be part of one or
66 both phases. O/w emulsions require antimicrobial agents because the aqueous phase is
favorable for the growth of micro-organisms. Preservatives that are commonly used in
emulsions include methyl-, ethyl-, propyl-, and butyl-parabens, benzoic acid, and quaternary
ammonium compounds. Antioxidants are required if the oil phase is an external phase of the
emulsion.
Preparation of the emulsion is comprised of several steps:
1. Preparation of the aqueous phase
2. Preparation of the oil phase
3. Emulsification
4. Homogenizing
Before preparing the emulsion, it is important to determine what type of emulsion is being
produced. The ratio of oil and aqueous phases and the type of emulsifier, are very important.
Ad 1. Preparation of the aqueous phase - all water soluble substances are dissolved in
water. In the case that the external phase is the aqueous phase, it is possible to add a substance
to the final emulsion. It is not recommended to add strong electrolytes to the final emulsion,
as the high concentration can break the emulsion.
Ad 2. Preparation of the oil phase - all hydrophobic substances are mixed together
(e.g. oils, fats, waxes, fatty acids, fatty alcohols) as well as substances soluble in the
hydrophobic phase.
Ad. 3 Emulsification is process where one phase is divided into small particles that are
dispersed simultaneously within the second phase. It is important that the temperature of the
phases should range from between 50 and 80C, depending on the nature of the product.
Emulsification can be carried out with mortar and pestle, shaking in the bottle, or using a
mixer or other mixing equipment.
Ad 4 Homogenization is a process using homogenizers where droplets of different
particle size in the primary emulsion are reduced to the desired size to ensure appropriate
stability of the preparation. For small volumes of products, this step can be skipped, or it can
be used a mixer.
67 Preparation according to incorporation of emulsifier we know several types of emulsification
techniques
1. English technique – wet gum method
This is suitable for the preparation of w/o and o/w emulsions. The emulsifier is incorporated
into the phase in which it is more soluble (EXTERNAL), in part or in whole.
o/w emulsions

If the proportion of oil and water and emulsifier are similar, the gum is dissolved
in the water part to form mucilage, then rest of the water is added, and finally oil is
slowly added in portions while being agitated.

If there is a smaller amount of the oil phase, the water phase is divided into two
parts. In the first part, the emulsifier is dissolved, and then the oil phase is slowly
added, so a concentrated emulsion is created. Finally, the concentrated emulsion is
diluted with the remaining water.
w/o emulsions

The emulsifier is dissolved in the external oil phase, and then the water phase is
gradually added while being agitated.
Liquid emulsions can be prepared by shaking them in the bottle. The size of the bottle should
correspond with the volume of the preparation and must be dry, or rinsed by the outer phase.
Rinsing the interior walls of the bottles with the inner phase can result in the creation of an
opposite type of emulsion.
2. Continental technique – dry gum method
Suitable for the preparation of o/w emulsions, it is used to prepare the emulsion from a
polymer or “gum” type emulsifier (gum arabic, tragacanth, gelatin or other emulsifiers from
the group of macromolecular solid substances). The emulsifier is incorporated into the phase
in which it is practically insoluble (INTERNAL). The emulsifier is dispersed in the oil and
part of the external aqueous phase is added to the resulting suspension (for each emulsifier is
an individual volume of aqueous phase to prevent formation of clusters) and is stirred
intensively. A viscous emulsion base is created (in this stage the emulsifier slowly dissolves
68 in the added water). Oil is then added by parts and finally the rest of water is slowly added
while stirring rapidly until the emulsion is completed (o/w).
The continental technique is used for the incorporation of emulsifiers, where, during the first
stage of preparation, the emulsion w/o is created, and then, after adding the rest of the
aqueous phase, it is changed into an emulsion o/w. This phase inversion allows for the
preparation of a stable emulsion with lower mechanical energy.
3. “In situ” soap method
This method is suitable for the preparation of emulsions w/o and o/w. The emulsifier is a
soap, which is formed as a result of the reaction between the components of the oil phase
(higher fatty acids, which are part of the oils and fats) with components of the aqueous phase alkali (emulsion o/w – sodium hydroxide, sodium, potassium, ammonium carbonate,
trolamin; emulsion w/o – calcium, magnesium, aluminium hydroxide). Some reactions can be
accelerated with heat.
4. Method using a complex emulsifier
This method is suitable for the preparation of emulsions o/w. Substances forming a complex
emulsifier can be prescribed separately or in a mixture. If emulsifiers are separate, the English
(wet gum) technique is used. Each emulsifier is incorporated into the phase in which it is
more soluble, i.e. a primary emulsifier into the aqueous phase and a secondary emulsifier into
the oil phase. If the emulsifiers are in the mixture, [e.g. Cetostearyl alcohol emulsificans (type
A) and (B)] the continental technique is used. The mixture of emulsifiers is incorporated into
the oil phase.
69 EXAMPLES
English technique – wet gum method
-
Procedure is the same as in the case of mucilage or gel preparation
 Exercise 1. 12.1
Rp.
Methylcellulosi
Glyceroli 85%
Paraffini liquidi
Foeniculi etherolei
Aq. purificatae
M. f. emulsio
D.S. one spoonful 2 times a day
ad
1.5
5.0
30.0
0.5
100.0
Preparation procedure: Use 2.5% mucilage of methylcellulose (calculate the amount of
methylcellulose mucilage). Add water to mucilage and homogenize. Finally, emulsify liquid
paraffin and foeniculi etheroleum.
Additional labels on package: Shake before use!
Shelf life: 14 days in the refrigerator
 Exercise 1.12.2
Rp.
Tragacanthae
Polysorbati 80
Glyceroli 85%
Paraffini liquidi
Aq. purificatae
ad
1.0
0.6
10.0
25.0
100.0
M. f. emulsio
D.S. one spoonful 2 times a day
Preparation procedure: Mix tragacanth with Polysorbate 80, glycerol and purified water.
Emulsify liquid paraffin into this mixture and homogenize.
70 Additional labels on package: Shake before use!
Shelf life: 14 days in the refrigerator
 Exercise 1.12.3
Rp.
Carmellosi natrici
Polysorbati 80
Paraffini liquidi
Aq. purificatae
1.0
0.5
20.0
100.0
ad
M. f. emulsio
D.S. one spoonful 2 times a day
Preparation procedure: Use 2.0% mucilage of carmellose (calculate the amount of carmellose
mucilage). Add Polysorbate and water to mucilage and homogenize. Finally, emulsify liquid
paraffin.
Additional labels on package: Shake before use!
Shelf life: 14 days in the refrigerator
Continental technique – dry gum method
 Exercise 1.12.4
Rp.
Vanillini
Ethanoli 96%
Sirupi simplicis
Carmellosi natrici
Polysorbati 80
Paraffini liquidi
Aq. purificatae
ad
M. f. emulsio
D. S. one spoonful 3 times a day
71 0.01
5.0
20.0
1.0
0.5
20.0
100.0
Preparation procedure: Mix solid carmellose with Polysorbate 80 and liquid paraffin. Add 12
g of purified water at once and mix rapidly and thoroughly as soon as you hear clicking
sound. Then add rest of purified water and sirupus simplex. Finally, admix vanilin in ethanol.
Additional labels on package: Shake before use!
Shelf life: 14 days in the refrigerator
 Exercise 1.12.5
Rp.
Methylcellulosi
Polysorbati 80
Helianthi olei
Sirupi simplicis
Aq. purificatae
ad
0.5
0.5
10.0
15.0
100.0
M. f. emulsio
D. S. one spoonful 3 times a day
Preparation procedure: Mix solid methylcellulose with Polysorbate 80 and sunflower oil. Add
12 g of purified water at once and mix rapidly and thoroughly as soon as you hear clicking
sound. Then add rest of purified water and sirupus simplex.
Additional labels on package: Shake before use!
Shelf life: 14 days in the refrigerator
“In situ” soap method
 Exercise 1.12.6
Rp
Acidi oleinici
Ammoniae sol. 10%
Helianthi olei
1.0
25.0
74.0
M. f. emulsio
D. S. ammonium liniment
72  Exercise 1.12.7
Rp.
Calcii hydroxidi sol.
Lini oleum
50.0
50.0
M. f. emulsio
D. S. calcium liniment
 Exercise 1.12.8
Rp.
Trolamini
Acidi oleici
Helianthi olei
Aq. purificatae
ad
2.5
5.0
20.0
100.0
M. f. emulsio
D. S. cleaning emulsion
 Exercise 1. 12.9
Rp.
Spiriti saponis kalini
Ammoniae sol. 10%
Camphorae
Ricini olei
Rapae olei
0.5
21.5
5.0
13.0
60.0
M. f. emulsio
D. S. camphor liniment
Preparation procedure:
Note for exercises 1. 10.6, 1.10.7, 1. 10.8 and 1. 10.9: Put all
ingredients into a dry bottle and shake. For shaking, use a 100 ml-volume bottle if you
prepare a 50 ml-volume emulsion!
Additional labels on package: Shake before use!
Shelf life: 1 month in the refrigerator
73 Method using a complex emulsifier
 Exercise 1.12.10
Rp.
Propylenglycoli
Neoaquasorbi
Helianthi olei
Paraffini liquidi
Polysorbati 80
Aq. conservantis
ad
2.5
5.0
5.0
3.0
1.0
100.0
M. f. emulsio
D. S. for external use
 Exercise 1.12.11
Rp.
Aurantii etherolei
Cholesteroli
Adipis lanae
Trolamini
Stearini
Cerae albae
Helianthi olei
Aq. purificatae
0.5
1.0
2.5
3.5
5.0
7.5
12.5
90.0
M. f. emulsio
D. S. for external use
 Exercise 1.12.12
Rp.
Paraffini liquidi
Alcoholi cetylici
Natrii laurylsulfatis
Aq. purificatae
49.0
1.0
1.0
….. 100.0
ad
M. f. emulsio
D. S. for external use
74 Preparation procedure: Note for exercises 1. 10.10, 1. 10.11 a 1. 10.12: A mixture containing
all the substances is heated in a beaker over a water bath (70ºC) until they are entirely melted.
The emulsion is prepared (homogenized) by hand, and mixed three times in one-minute
intervals with 30-second breaks. Volatile substances (essential oils) are then added to the final
emulsion.
Additional labels on package: Shake before use!
Shelf life: 1 month in the refrigerator
75 1.13 Suspensions
Suspensions are (at least) two-phase systems consisting of a finely divided solid (inner phase)
dispersed into a liquid vehicle (outer phase).
In these preparations, the substance distributed is referred to as the dispersed phase and the
vehicle is known as the dispersing phase or dispersion medium. Together, they form a
dispersed system (the term refers to a system in which one substance (dispersed phase) is
distributed as discrete particles, throughout a second substance (continuous phase or vehicle)).
Suspensions are liquid dosage forms intended for oral, topical and parenteral application. In
many dosage forms can be the active ingredient(s) suspended in a suitable vehicle (ointments,
creams, suppositories, etc.). The absorption of the drug from the suspension (after p.o.
application) is faster than that from solid dosage forms, but slower than those absorbed from
solutions.
Solid particles in the form of a pharmaceutical suspension should be homogeneously
dispersible after shaking, they should have the desired, constant particle size and
sedimentation after shaking should start only after the time needed to administer the dosage (≈
2 min).
Suspensions are usually coarse dispersed systems, which come through physical changes
depending on time. The stability of the preparation is affected by solid particle size, surface
wettability of solids by liquid vehicle and viscosity of the outer phase.
Basic properties of suspensions
 Liquid, easy application
 Accurate dosing and expected therapeutic effect
 Slow sedimentation (= settle)
 Easy sediment re-shaking (re-suspendation)
 Duration and onset of action can be controlled
 Constant particle size
 Pleasant appearance
76  Resistant to microbial contamination
Excipients
 Liquid media – water, ethanol, glycerol, propylene glycol, plant oils, liquid paraffin
 Viscosity-increasing agents (thickeners) – water dispersion of colloidal silicon
dioxide, bentonite magma, mucilages of macromolecular materials (cellulose
derivatives, gums)
 Substances to improve surface wettability – surfactants, ethanol, glycerol,
propylene, glycol
 Substances to improve flocculation – electrolytes, surfactants, polymers
 Substances to adjust pH value – buffers, citric acid
 Antimicrobial preservatives – paraaminobenzoic acid derivatives (parabens),
carbethopendecinium bromide, ethanol
 Antioxidants – propyl gallate, tocoferol acetate
 Taste and smell-improving agents – syrups, sweeteners, aromatic waters
 Colours
Classification of suspensions according to:
Method of Application
1. Oral suspensions (Mixturae)
2. Topical suspensions
- Suspension lotions (Lotiones suspensae)
- Liquid powders (Pulveres adspersorii liquidi)
77 Surface wettability and quality of solvating surface
Non-flocculated
Flocculated
perfect
good
bad
+
+
-
Supernatant
cloudy
bright
Sediment
small
large
increasing in time
decreasing in time
not easy „caking“
not problematic
Wettability
Pharmaceutical applicability
Sediment re-shaking
Floated
impossible
General methods of suspension preparation
1. Dispersion of solid substance in liquid medium
a) Solid phase preparation
 Crushing, grinding or milling of solid materials to the required particle size
(topical preparations 10 – 100µm, oral suspensions < 200µm).
 Sieving, homogenization.
b) Liquid phase preparation
 Dissolving of soluble active substances and excipients in a liquid medium.
c) Dispersion

Liquid phase is slowly added (in parts !!!) to powders by continual mixing in
mortar and pestle (initially a prepared concentrated suspension is used, which
is subsequently diluted).
 Semi-solids immiscible with water (tars, etc.) should be first dissolved in a technical
auxiliary substance (ether, acetone), then a mixture of powders should be added. This
blend should be mixed until completely evaporated (working in fume hood) of organic
solvent (absorption of semisolid material on the surface of solid particles).
78  Volatile solid substances (menthol, camphor) should be added to solid particles after
dissolving in small amount of solvent (ethanol).
 Liquid ingredients immiscible with water (oils, paraffins) should be emulsified into
the completed suspension.
 Drugs soluble in the outer phase should be added in step (b) or at the end of the
preparation procedure.
2.
Condensation
The group of methods based on the principle of the crystallization of the substance from its
molecular or ionic dispersion by:
a) Temperature change
b) Solvent change
c) pH value change
d) Chemical reaction (active substance is different from entry materials!)
Packaging
Packaging is specific for each type of preparation and administration method (usually narrow
or wide-neck bottles). There must be an extra space of packaging reserved for the shaking of
the suspension before use.
Labels
 Basic labels
o Colour (white – oral, injection; red – topical; yellow – laboratory reagents)
o Label requirements (information for the patient, dosage, date, address of
pharmacy, signature, expiration, quantity)
 Additional labels - important notices
o Shake before use! Corrosive! Flammable! For animals only! Poison!
o Storing conditions (Keep out of light!; Keep cold!)
Shelf life
 Shelf life is specified by the pharmacist with respect to:
79 o National authorities´ recommendations
o Scientific literature
o Physico-chemical and microbiological stability
o Duration of therapy
For most prepared pharmaceutical suspensions, there is a maximum shelf life of 1 month if
they are antimicrobially protected (preservatives) or are prepared from non-aqueous solvents.
Shelf life is only 1 week for water antimicrobially non-protected preparations (2 weeks,
when stored in cold conditions).
Note: Use stainless steel mortar and ceramic pestle when using coloured substances (coal tar,
bismuth tribromphenolate, etc.)
EXAMPLES
 Exercise 1.13.1
Zinci oxidi suspensio – Suspension of zinc oxide
Zinci oxidum (45)
Talcum (45)
Glycerolum 85%
Bentoniti magma
25.0
25.0
25.0
25.0
M. f. suspension
Preparation procedure: Admix the blend of ZnO and talc in glycerol. Slowly add bentonite
magma.
Additional labels on package: Shake before use!
Storage conditions: Store in wide-neck bottle.
 Exercise 1.13.2
Sulfuris suspensio – Sulphur suspension
Sulfur ad usum externum
Ether solvens
Ethanolum 60%
2.5
12.5
12.5
M. f. suspension
80 Preparation procedure: Add mixture of alcohol and ether to sulphur. Work in close-neck
bottle.
Additional labels on package: Shake before use! Inflammable!
Storage conditions: Cold place (8-15°C).
Shelf life: 1 month
Dispensing: Apply a piece of cotton-wool to the mouth of the bottle when shaking and apply
on the desire area.
 Exercise 1.13.3
Rp.
Magnesii oxidi
Acaciae mucilaginis
Aq. purificatae
ad
10.0
5.0
100.0
M. f. suspension
D. S. 3 x 1 spoonful
Preparation procedure: Prepare acaciae mucilage according to pharmacopoiea. (33% GA in
Aqua conservans). Suspend magnesium oxide in this mucilage and dilute the concentrated
suspension with the rest of the water.
Adjustment: narrow-neck bottle
Additional labels on package: Shake before use!, c.p.
Storage conditions: cold place (8-15°C)
Shelf life: 1-2 weeks
 Exercise 1.13.4
Rp.
Calcii carbonatis
Bismuthi subnitratis
Methylcellulosi mucilago
Aq. purificatae
M. f. suspensio
D. S. 3 x 1 spoonful
ad
81 1.0
1.0
20.0
100.0
Preparation procedure: Use 2.5% methylcellulose mucilage. Disperse the powder mixture in
this mucilage and add of the remaining water.
Adjustment: narrow-neck bottle
Additional labels on package: Shake before use!
Storage conditions: cold place (8-15°C)
Shelf life: 1-2 weeks
 Exercise 1.13.5
Rp.
Calcii chloridi
Natrii hydrogenocarbonatis
Aq. purificatae
ad
4.0
6.25
50.0
M. f. suspensio
D. S. Use between meals
Preparation procedure: Mix two solutions – a prepared 50% solution of calcium chloride and
solution of sodium hydrogencarbonate in water. Add the remaining water. The active
substance is formed by chemical reaction
Additional labels on package: Shake before use!
Shelf life: 1-2 weeks
82  Exercise 1.13.6
Rp.
Bismuthi tribromphenolatis
Balsami peruviani
Ricini olei
M. f. suspensio
D. S. Visnevski balm
1.0
4.0
15.0
Preparation procedure: Admix the solid substance in a small amount of castor oil, then add
the rest of the oil and balsam of Peru. Work in a stainless steel mortar.
Adjustment: wide-neck bottle
Additional labels on package: Shake before use!
Shelf life: 3 months
 Exercise 1.13.7
Rp.
Picis lithantracis
Zinci oxidi
Talci
Glyceroli 85%
Aerosoli dispersii
ad
1.5
20.0
20.0
15.0
100.0
M. f. suspensio
Preparation procedure: Dissolve coal-tar in 7.5g of ether in one dish. Mix the powders in
another dish. Then add this mixture to the dissolved tar and mix it in a fume hood until all of
the ether has evaporated. Then add glycerine and the dispersion of silica dioxide. Work in a
stainless steel mortar.
Adjustment: wide-neck bottle
Additional labels on package: Shake before use!
Shelf life: 1 month
83  Exercise 1.13.8
Rp.
Ichthamoli
Zinci oxidi
Talci
Calcii carbonatis
Glyceroli 85%
Aerosoli dispersii
ad
0.5
10.0
10.0
10.0
15.0
100.0
M. f. suspensio
Preparation procedure: Prepare a powder mixture of zinc oxide, talc and calcium carbonate.
Add glycerine and the silica dioxide dispersion and then ichtammolum (hydrophilic liquid).
Adjustment: Wide-neck bottle
Additional labels on package: Shake before use!
Shelf life: 1 month
 Exercise 1.13.9
Rp.
Mentholi
Zinci oxidi
Talci
Glyceroli 85%
Ethanoli 96%
Aerosoli dispersii
ad
1.0
20.0
20.0
15.0
20.0
100.0
M. f. suspensio
Preparation procedure: Dissolve menthol in ethanol, add the powder mixture, then the
glycerol and dispersion of silica dioxide.
Adjustment: Wide-neck bottle
Additional labels on package: Shake before use!
Shelf life: 1 month
84  Exercise 1.13.10
Rp.
Tannini
Boli albi
Talci
Helianthi olei
Aerosoli dispersii
2.0
aa
ad
10.0
2.5
100.0
M. f. suspensio
Preparation procedure: Mix a powder mixture of tanninum, white clay and talc with a
dispersion of silica dioxide and then emulsify sunflower oil (three-phase system).
Note: Add 0.5g of Polysorbate before adding Sunflower oil.
Adjustment: Wide-neck bottle
Additional labels on package: Shake before use!
Shelf life: 1 month
85 2.
Semi-solid preparations
Semi-solid preparations for cutaneous applications are intended for local or transdermal
delivery of active substances, and for their emollient or protective action. They are also of
homogeneous appearance. The preparations usually consist of either a simple or compound
base in which one or more active substances are dissolved or dispersed. According to its
composition, the base may influence the activity of the preparation.
The base may consist of natural or synthetic substances and may be single phase or multiphase. According to the nature of the base, the preparation may have either hydrophilic or
hydrophobic properties; it may contain suitable excipients such as antimicrobial preservatives,
antioxidants, stabilisers, emulsifiers, thickeners and penetration enhancers.
Semi-solid preparations for cutaneous applications intended for use on severely injured skin
must be sterile.
Categories of semi-solid preparations for cutaneous applications
 Ointments
 Creams
 Gels
 Pastes
 Poultices (cataplasma)
 Medicated plasters
According to their structure, ointments, creams and gels generally show a viscoelastic
behaviour and are non-Newtonian in character, e.g. plastic, pseudoplastic or thixotropic types
flow at high shear rates. Pastes frequently exhibit dilatancy.
Characteristics of individual semisolids
 Ointments (unguenta)
86 Definition
An ointment consists of a single-phase base in which solids or liquids may be dispersed.
o Hydrophobic ointments
Hydrophobic ointments can absorb only small amounts of water. Typical bases used for their
formulation are hard, liquid and light liquid paraffins, vegetable oils, animal fats, synthetic
glycerides, waxes and liquid polyalkylsiloxanes.
o Water-emulsifying ointments
Water-emulsifying ointments can absorb larger amounts of water and can thereby produce
water-in-oil or oil-in-water emulsions after homogenisation, depending upon the nature of the
emulsifiers. Water-in-oil emulsifying agents such as wool alcohols, sorbitan esters,
monoglycerides and fatty alcohols, oil-in-water emulsifying agents such as sulfated fatty
alcohols, polysorbates, macrogol cetostearyl ether or esters of fatty acids with macrogols may
be used for this purpose. Their bases are the same as those of hydrophobic ointments.
o Hydrophilic ointments
Hydrophilic ointments are preparations that have bases that are miscible with water. The
bases usually consist of mixtures of liquid and solid macrogols (polyethylene glycols), and
may contain an appropriate amount of water.
 Creams (cremores)
Definition
Creams are multi-phase preparations that consist of a lipophilic phase and an aqueous phase.
o Lipophilic creams
Lipophilic creams have as their continuous phase, the lipophilic phase. They usually contain
water-in-oil emulsifying agents such as wool alcohols, sorbitan esters and monoglycerides.
o Hydrophilic creams
Hydrophilic creams have as their continuous phase, the aqueous phase. They contain oil-inwater emulsifying agents such as sodium or trolamine soaps, sulfated fatty alcohols,
87 polysorbates and polyoxyl fatty acid and fatty alcohol esters combined, if necessary, with
water-in-oil emulsifying agents.
 Gels (gelata)
Definition
Gels consist of liquids gelled by suitable gelling agents.
o Lipophilic gels
Lipophilic gels (oleogels) are preparations whose bases usually consist of liquid paraffin with
polyethylene or fatty oils, gelled with colloidal silica, aluminium or zinc soaps.
o Hydrophilic gels
Hydrophilic gels (hydrogels) are preparations whose bases usually consist of water, glycerol
or propylene glycol gelled with suitable gelling agents such as poloxamers, starch, cellulose
derivatives, carbomers or magnesium-aluminium silicates.
 Pastes (Pastae)
Definition
Pastes are semi-solid preparations for cutaneous applications containing large proportions of
solids finely dispersed in the base.
 Poultices (Cataplasma)
Definition
Poultices consist of a hydrophilic heat-retentive base in which solid or liquid active
substances are dispersed. They are usually spread thickly on a suitable dressing and heated
before applying to the skin.
88  Medicated plasters (Emplastra medicata)
Definition
Medicated plasters are flexible preparations containing one or more active substances. They
are intended to be applied to the skin. They are designed to keep the active substance(s) in
close contact with the skin so that they may be absorbed slowly, or act as a protective or
keratolytic agent.
 Semi-solid eye preparations (Ocularia semisolida)
Definition
Semi-solid eye preparations are sterile ophthalmic ointments, creams or gels designed for
application to the conjunctiva, and contain one or more active substances dissolved or
dispersed in a suitable base which does not irritate the conjunctiva. They have a homogeneous
appearance.
Semi-solid eye preparations are packed in small, sterilised collapsible tubes fitted or provided
with a sterilised cannula. The containers contain at most 10 g of the preparation, unless
otherwise justified and authorised. The tubes must be closed tightly to prevent microbial
contamination. The containers, or the nozzles of tubes, are of such a shape as to facilitate
administration without contamination.
 Semi-solid nasal preparations (Nasalia semisolida)
Definition
Semi-solid nasal preparations (ointments, creams, gels, and pastes) are intended for
application into the nasal cavity, and consist of simple or compound bases, in which one or
more drugs are usually dissolved or dispersed. Hydrophilic semi-solid preparations are more
suitable for nasal application because of the favorable effect on the ciliated epithelium of the
mucosa. Therefore, it it preferred that:
-
Hydrophilic ointment consisting of polyethylene glycols with different molecular
weight hydrophobic ointments, especially those that have hydrocarbon bases, should
be used only in rare cases,
89 -
Hydrophilic creams, which are emulsion preparations o/w,
-
Hydrogels, which are dispersions of polymer substances (e.g., cellulose derivatives,
polyacrylic acid derivatives, etc.) in water, or other hydrophilic solvent.
 Semi-solid ear preparations (Auricularia semisolida)
Definition
Semi-solid ear preparations are ointments, creams, gels or pastes intended for application to
the external ear, auditory meatus, or tampons impregnated with the preparation. They are
supplied in containers fitted with a suitable applicator. Depending on the nature of the base
(constitutive excipient) they may have hydrophilic or lipophilic properties, and may also
contain other ingredients (such as antimicrobial agents, antioxidants, emulsifiers, etc.).
 Semi-solid rectal preparations (Rectalia semisolida)
Definition
Semi-solid rectal preparations are ointments, creams or gels. They are often single-dose
preparations in containers with a suitable applicator.
 Semi-solid vaginal preparations (Vaginalia semisolida)
Definition
Semi-solid vaginal preparations are ointments, creams or gels. They are also single-dose
preparations in containers with a suitable applicator.
 Semi-solid oral preparations (Oromucosalia semisolida)
Definition
Semi-solid oral preparations are hydrophilic gels or pastes intended for use in the oral cavity
or in specific parts of the oral cavity, such as gingiva (gel on the gingiva, gingiva paste).
They may also be in the form of single-dose products.
90 Basic requirements for the preparation (manufacture) of semi-solid dosage
forms
General methods of preparation
Appropriate ways to ensure the microbial quality of semi-solid preparations for cutaneous
application are used during the preparation (manufacturing), packaging, storing and
dispensing (distribution); recommendations for this are provided in Microbiological quality of
pharmaceutical preparations (Ph. Eur).
Sterile drugs (Category 1 of microbiological quality of medicinal products) are produced
using materials and methods designed to ensure sterility and to avoid the introduction of
contaminants and the growth of micro-organisms; recommendations for this are provided in
Methods of preparation of sterile products (Ph. Eur).
Conditions for other (non-sterile) preparations must ensure that the quality of the drugs
fulfill the criteria for Category 2 (preparations for local use and for use in the respiratory tract)
or Category 3 (products for oral and rectal use) of the microbiological quality of drug
preparations.

Preparation (manufacture) of semi-solid dosage forms must be carried out
according to the guidelines (see below for general steps of preparation of
semi-solid dosage forms).

Preparation of semisolid drugs in the pharmacy follows the principles of
good manufacture practice (Public notice no. 255/2003) (See liquid
preparations).
Quality evaluation
In the manufacture of semi-solid preparations for cutaneous application, suitable measures
should be taken to ensure that the defined rheological properties will be fulfilled. Where
appropriate, the following non-mandatory tests should be carried out: measurement of
consistency by penetrometer, viscosity (apparent viscosity) and a suitable test to demonstrate
the appropriate release of the active substance(s).
Final semi-solid preparations are tested according to Czech Pharmacopoeia 2009:
91 
Test for extractable mass or volume – performed in the semi-solid preparations
in single-dose containers,

Sterility – performed in ophthalmic preparations and preparations labeled as
sterile,

Particle size – performed in semi-solid suspension ophthalmic preparations,

Uniformity of content – performed in single-dose eye and ear preparations
containing drugs in the content less than 2 mg or less than 2% of the total weight,

Content evaluation – peformed for individual products.

Uniformity of weight – performed in single-dose eye and ear preparations,

Identification tests – performed for individual preparations,

Purity test – performed for individual preparations,
Labels
In addition to information required for all preparations, the label shall state:
-
Where appropriate, that the product is sterile (i.e. in the case of dosage forms that may
not be sterile basically)
-
For single-dose eye preparations – that the content is intended only for one usage,
-
In multi-dose eye and ear preparations - that after first opening the product, it must be
used during a four-week period, (after which the content may not be used) if it is not
approved or determined otherwise.
Packaging
All semi-solid preparations should be stored in well-sealed containers. If the product contains
water or other volatile substances, it must be stored in airtight containers. When the product is
sterile, it must be stored in secure, sterile, airtight containers.
In the pharmacy, preparations are usually packed in plastic cups or wide-necked bottles with
screw caps. Semi-solid eye preparations are packed into small, sterilized, squeezable tubes
(metal or plastic) with a capacity of not more than 5g. The tubes must be closed and have an
applicator that ensures an uncontaminated application.
92 Because of the nature of active excipients, they may require protection from light and/or
storage at lower temperatures (cold or refrigerated). These preparations are prepared in the
pharmacy for time of need (individual production) or stocks (collective production). The
shelf-life of some of these products is determined by the State Institute for Drug Control
(SÚKL) recommendations (see the current table in the laboratory). For other preparations, the
pharmacist determines the shelf-life according to the nature and length of treatment for up to 1
month.
93 2.1
Ointments
One-phase hydrophobic ointments without drugs – ointment bases
One-phase hydrophobic ointments are usually prepared by the melting of all components
(including emulsifiers), preferably in an enamel mortar over a water bath, or under infrared
lamps. The mixture of all of the substances is melted all at once or by melting the substances
at the highest melting point and then adding more substances. If necessary, the melted mixture
is filtered through several layers of gauze to get rid of the impurities, and stirred while
continually scraping the mixture from the walls of the mortar. If the base contains a waxy
substance nature (beeswax, hard paraffin wax, stearin, etc.) do not accelerate the cooling
process by putting it in water or ice. This will change the consistency of the final product,
making it more stiff and non-homogenous than desired.
Pharmacopoeal ointments: Alcoholis cetylici unguentum, Alcoholum adipis lanae
unguentum, Unguentum constituens pro antibioticis, Unguentum emulsificans anionicum,
Unguentum emulsificans nonionicum, Unguentum, Unguentum ophtalmicum simplex,
Unguentum simplex.
EXAMPLES
Pharmacopoeal formulas
 Exercise 2.1.1
Alcoholis cetylici unguentum
Alcohol cetylicus
Adeps lanae
Vaselinum album
2.0
15.0
83.0
Preparation procedure: Cetyl alcohol, wool fat and white Vaseline are melted; then the
mixture is stirred until cool.
Storage: Protect from light
94  Exercise 2.1.2
Alcoholum adipis lanae unguentum
Alcoholes adipis lanae
Vaselinum flavum
10.0
90.0
Preparation procedure: Alcoholes adipis lanae and yellow Vaseline are melted; then the
mixture is stirred until cool.
Storage: Protect from light.
 Exercise 2.1.3
Unguentum constituens pro antibioticis
Adeps lanae
Paraffinum liquidum
Vaselinum flavum
10.0
10.0
80.0
Preparation procedure: Adeps lanae, liquid paraffin, yellow Vaseline are melted and then
mixed. The mixture is then filtered through a gauze and sterilized in a stream of hot air for 90
minutes at 140C.
Storage: Protected from light and store at a temperature from 8 - 15C.
Dispenzing: After opening, the ointment base must be used within 48 hours. It is used only for
the preparation of ointments with bacitracin, erythromycin, oxytetracycline, tetracycline,
chloramphenicol or other antibiotics , provided they are checked for stability.
 Exercise 2.1.4
Unguentum emulsificans nonionicum
Polysorbatum 60
Alkohol cetylstearylicus
Paraffinum liquidum
Vaselinum album
10.0
30.0
10.0
50.0
Preparation procedure: Polysorbate 60, cetostearyl alcohol, liquid paraffin and white Vaseline
are melted and stirred until they have cooled.
Storage: Protect from light
95  Exercise 2.1.5
Unguentum ophtalmicum simplex
Adeps lanae
Paraffinum liquidum
Vaselinum album
10.0
10.0
80.0
Preparation procedure: Adeps lanae, liquid paraffin and white Vaseline are melted and then
mixed. The mixture is then filtered through three layers of gauze, poured into containers
suitable for sterilization and then sterilized with dry heat for 2 hours at 160 C. The semicooled, sterilized ointment is agitated in the clean room of grade A and poured into suitable
containers.
Storage: Protect from light
 Exercise 2.1.6
Unguentum simplex
Propylis gallas
Ethanol 96% (V/V)
Adeps suilus
Alcohol cetylicus
Cera alba
0.01
1.0 ml
90.0
5.0
5.0
Preparation procedure: Cetyl alcohol, white wax and lard are melted over a water bath at
70C, and then propyl gallate, dissolved in 96% ethanol, is added dropwise and stirred until
cool.
Storage: Protect from the light.
One‐phasesolutionhydrophobicointments
Method of preparation
1.
One-phase solution hydrophobic ointments are prepared by dissolving the drug
in the ointment base at room temperature – this method is used when the
prescribed drugs form an eutectic mixture (menthol, camphor, β naphthol, phenol,
etc.) or when adding hydrophobic or volatile substances (e.g., methyl salicylate,
essential oils) to the base.
96 2.
By dissolving the drug in the ointment base at higher temperature – this method is
used when it is known that all the drugs that are dissolved in the melted base have
remained dissolved after cooling and during storage. The stability of the drug at higher
temperature is very important. E.g., when there are incorporate volatile substances
used, such as menthol or camphor, these must be dissolved in a warm base (max. of
40°C), and then stirred until they have cooled down.
3.
By dissolving the drug in an auxiliary liquid/volatile solvent and then mixing with
the ointment base
Hydrophobic liquid (vegetable oil, liquid paraffin) is used as an excipient, which may be part
of the formula, or may replace some of the hydrophobic component.
A volatile organic solvent (ether) may also be used as an excipient, and evaporates after being
mixed with an ointment base.
EXAMPLES
 Exercise 2.1.7
Rp.
Mentholi
Unguentum lanalcoli
ad
2.0
50.0
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Menthol is comminuted. Unguentum lanalcoli is melted over water
bath at 40 ºC and then added to comminuted menthol. Finally, mixture is stirred until cool.
 Exercise 2.1.8
Rp.
Camphorae
Vaselini albi
1.5
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
97 Preparation procedure: Camphor is comminuted. White Vaseline is melted over water bath at
40 ºC and then is added to comminuted camphor. Finally, mixture is stirred until cool.
 Exercise 2.1.9
Rp.
Mentholi
Methylis salicylatis
Vaselini albi
2.25
4.5
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Menthol and methylis salicylas are comminuted together – creation of
eutectic mixture. White Vaseline is melted over water bath at 40 ºC and then added to eutectic
mixture. Finally, mixture is stirred until cool.
 Exercise 2.1.10
Rp.
Sinapis etherolei artificialis
Mentholi
Camphorae
Eucalypti etherolei
Vaselini albi
ad
0.5
1.0
3.0
0.5
50.0
M. f. ung.
D. S apply ointment to the skin
Preparation procedure: Sinapis etheroleum, mentol, camphor and eucalyptum etheroleum are
comminuted together – creation of eutectic mixture White Vaseline is melted over water bath
at 40 ºC and then added to eutectic mixture. Finally, mixture is stirred until cool.
Two‐phasesuspensionhydrophobicointments
Method of preparation
1. Comminution of drugs (adjusting particle size) – a rough mortar with pestle is used in
the pharmacy, followed by straining through a sieve of appropriate mesh size (if the
drug amount is less than ten grams). When comminuting higher amounts, suitable
98 milling equipment can be used. If there is a combination of several drugs, a
homogenous blend is created after comminution (following straining through the
already adjusted to the appropriate particle size (e.g. sulfur for external use with a
maximum particle size of 40 m). These drugs do not have to be comminuted.
2. Premixing drugs – the premixing of drugs is accomplished with a small amount (1:1,
1:0.5) of liquid paraffin, or a liquid component of ointment base, or, with the ointment
base itself at room temperature, or melted. Some surfactants (usually emulsifiers w/o)
are also suitable. Premixing cannot be carried out in a liquid where the drug may be
more soluble than when in the ointment base. This is to avoid any subsequent
recrystallization. with the resulting particles irregularly distributed and their size
exceeding the permitted level. The aim of this operation is to prevent the emergence of
clusters of drug particles, and aid in the preparation of more finely powdered drugs.
When incorporating small quantities of drugs, in order to prevent loss from the
adherence to the walls of the mortar, pestle, and sieve, comminution and premixing is
carried in an oil or ointment base in the mortar.
3. Mixing of the premix suspension with the ointment base – to the premix suspension
is gradually added the ointment base (in parts). Generally, it is desirable to mix
approximately equal amounts (weight) together. If the suspension ointment is prepared
at a higher temperature, the mixture must be stirred until it begins to congeal. Quality
ointments are prepared by diluting the concentrated suspension ointments (e.g. 10%
boric ointment, 50% salicylic ointment, etc.)
Pharmacopoeal ointments: Acidi borici unguentum 10%, Acidi salicylici unguentum 10%,
Jecoris aselli unguentum compositum, Unguentum Whitfield, Zinci oxidi unguentum.
EXAMPLES
 Exercise 2.1.11
Acidi salicylici unguentum 10%
Acidum salicylicum (180)
Paraffinum liquidum
Vaselinum flavum
5.0
2.5
42.5
99 Preparation procedure: Salicylic acid is premixed with liquid paraffin. About 10g of melted
Vaseline is added to this mixture, homogenized, and then the remaining Vaseline is added.
Stir until cool or homogenized.
Storage: Protect from light.
Dispensing: If the doctor prescribes Acidi salicylici unguentum and does not specify the
concentration, we dispense with 1% ointment. This concentration is adjusted with yellow
Vaseline.
 Exercise 2.1.12
Unguentum Whitfield
Acidum salicylicum (90)
Acidum benzoicum (90)
Adeps lanae
2.5
6.0
41.5
Preparation procedure: To the mixture of salicylic and benzoic acid is with constant mixing
added adeps lanae which is melted over a water bath and then stirred until cool.
Storage: Protect from light and store at 8 - 15C.
 Exercise 2.1.13
Rp.
Acidi salicylici
Ung. simplicis
1.0
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Acidum salicylicum is premixed with part of the molten base (it is
also possible to premix the drug with sunflower oil, which is added at the expense of
unguentum simplex). With constant mixing, unguentum simplex is added to the mixture,
which is melted over a water bath and then stirred until cool.
100  Exercise 2.1.14
Rp.
Zinci oxidi
Jecoris aselli olei
Cerae albae
Adipis lanae
Vaselini flavi
10.5
15.0
2.0
5.0
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Zincum oxidum is premixed with jecoris aseli oleum. Cera alba,
adeps lanae and White Vaseline are melted over water bath and with constant mixing are
added to the mixture, then stirred until cool.
 Exercise 2.1.15
Rp.
Hydrargyri amidochloridi
Cerae albae
Adeps lanae
Vaselini albi
5.0
4.0
4.5
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Hydrargyrum amidochloridum is premixed with a part of the molten
base (it is also possible to premix the drug with liquid paraffin, which is added at the expense
of White Vaseline). Cera alba, adeps lanae and White Vaseline are melted over water bath and
with constant mixing are added the mixture, then stirred until cool.
Ointment must not be prepared in a stainless steel mortar!
101  Exercise 2.1.16
Rp.
Hydrargyri amidochloridi
Acidi salicylici
Ung. simplicis
0.5
0.75
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Hydrargyrum amidochloridum and acidum salicylicum are premixed
with a part of the molten base (it is also possible to premix drugs with sunflower oil, which is
added at the expense of unguentum simplex). Unguentum simplex is melted over a water bath
and with constant mixing is added to the mixture, then stirred until cool.
Ointment must not be prepared in a stainless steel mortar!

Exercise 2.1.17
Rp.
Acidi salicylici
Lavandulae etherolei
Syndermani
Vaselini flavi.
aa ad
1.0
1.0
50.0
M. f. ung
D. S. apply ointment to the skin
Preparation procedure: Acidum salicylicum is premixed with a part of the molten base (it is
also possible to premix the drug with liquid paraffin, which is added at the expense of Yellow
Vaseline). Synderman and Yellow Vaseline are melted over a water bath and with constant
mixing are added to the mixture, then stirred until cool. Finally, levandulae etheroleum is
added.
Two‐phaseemulsionhydrophobicointments
Hydrophobic emulsifying ointment bases containing emulsifiers are usually used to prepare
two-phase emulsion ointments. A liquid or drug solution is added to the base (lard) at room
102 temperature while stirring continuously. Generally up to 5% of the drug solution is added to
the base. If the nature of the base requires complete melting (hard paraffin, beeswax, waxy
emulsifiers, etc.), the mixture is stirred until partially cooled, typically to a temperature of
from 40-50C, and then the solution is emulsified into the base. This prevents the excessive
evaporation of water from highly concentrated drug solutions and also the creation of
supersaturated solutions, which are undesirable from the view of stability of the preparation.
Small amounts of concentrated aqueous solutions of drugs (1-2 g) are often added to the
emulsifying ointments and in these cases, in order to avoid significant loss, the drug is
dissolved directly in the mortar, and the resulting solution is added to the ointment base.
Pharmacopoeal ointments: Argenti nitratis unguentum compositum, Ichthamoli unguentum,
Unguentum molle.
EXAMPLES
Pharmacopoeal formulas
 Exercise 2.1.18
Ichthamoli unguentum
Ichthamolum
Aqua purificata
Alcoholum adipis lanae unguentum
5.0
2.5
42.5
Preparation procedure: Ichthamol is mixed with hot, purified water; after cooling, the purified
water is added to make 15g, and the solution is then gradually incorporated into alcoholum
adipis lanae unguentum.
Storage: Protect from light!
 Exercise 2.1.19
Unguentum molle
Adeps lanae
Paraffinum liquidum
Vaselinum flavum
Aqua purificata
32.5
3.75
25.25
5.0
103 Preparation procedure: Adeps lanae, liquid paraffin, and yellow Vaseline are melted over the
water bath, then purified water, pre-heated to 70C is admixed and mixed until cool. Then
water is added to make 100g and after 12 hours the final ointment is mixed.
Storage: Protect from light and store at 8 - 15C.
Dispensing: Before using or dispensing, the ointment must be stirred.
Examples of formulas
 Exercise 2.1.20
Rp.
Argenti nitratis
Aq. purificatae
Adipis lanae
Balsamum peruvianum
Ricini oleum
Vaselinum flavum
0.5
0.5
1.5
5.0
5.0
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Yellow Vaseline and adeps lanae are melted over water bath.
Argentum nitras is dissolved in the purified water and then is emulsified into the cooled base.
Balsamum peruvianum is premixed with ricinum oleum (1:1) and this blend is mixed with the
cooled base containing argentum nitras.
 Exercise 2.1.21
Rp.
Hydrogenii peroxidi 30%
Adipis lanae
Syndermani
2.5
6.0
20.0
ad
M. f. ung.
D. S. Whitening ointment
Preparation procedure: Synderman and adeps lanae are melted over water bath. Hydrogenii
peroxide 30% is emulsified into the cooled base.
104  Exercise 2.1.22
Rp.
Acidi borici
Aq. purificatae
Glyceroli 85%
Adipis lanae
Vaselini albi
0.075
2.425
2.5
10.0
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Vaselinum flavum and adeps lanae are melted over water bath. Cooled
base is mixed with reserve source of acidi borici unguentum 3% (calculate the amount of
reserve source of unguentum acidi borici 3%). Glycerol and purified water are then emulsified
into the base.
Threephasesuspension‐emulsionhydrophobicointments
In the preparation of three-phase hydrophobic ointments, it usually begin by suspending the
solids and hydrophobic parts of the base, including emulsifiers, and thus, a suspension
ointment is created (see the two-phase suspension hydrophobic ointments) in which the
hydrophilic liquid is emulsified (see the two-phase emulsion hydrophobic ointments).
EXAMPLES
 Exercise 2.1.23
Rp.
Acidi salicylici
Urae
Aq. purificatae
Syndermani
aa
2.5
3.5
25.0
ad
M. f. ung.
D. S. For treating warts
Preparation procedure: Acidum salicylicum is premixed with a part of the molten base (it is
also possible to premix the drug with liquid paraffin, which is added at the expense of
105 synderman). With constant mixing, the rest of synderman is added to the mixture, which is
melted over a water bath and then stirred until cool. Urea is dissolved in purified water and
mixture is finally emulsified into the base by parts.
 Exercise 2.1.24
Rp.
Tincturae carbonis detergentis
Hydrargyri amidochloridi
Olivae olei
Aq. purificatae
Adipis lanae
2.5
5.0
10.0
7.5
25.0
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Hydrargyrum amidochloridum is premixed with olive oil. With
constant mixing, adeps lanae is added to the mixture, melted over a water bath and then
stirred until cool. Purified water and tinctura carbonis detergents are then emulsified into the
ointment, separately.
Ointment must not be prepared in a stainless steel mortar!!!!
Exercise 2.1.25
Rp.
Acidi salicylici
Ichthamoli
Vaselini flavi
Ung. simplicis
aa
1.0
aa ad
50.0
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Acidum salicylicum is premixed with part of the molten base (it is also
possible to premix the drug with liquid paraffin, which is added at the expense of yellow
Vaseline or with sunflower oil, which is added at the expense of unguentum simplex). Yellow
Vaseline and unguentum simplex are melted over a water bath together and with constant
106 mixing are added to the mixture, then stirred until cool. Finally, ichthamol is emulsified into
the ointment.
 Exercise 2.1.26
Rp.
Amyli tritici
Zinci oxidi
Jecoris aselli olei
Adipis lanae
Aq. purificatae
Vaselini albi
2.5
2.5
10.0
7.5
5.0
22.5
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Wheat starch and zinc oxide are premixed with fish oil. White
Vaseline and adeps lanae are melted over water bath and with constant mixing are added to
the mixture, then stirred until cool. Finally, purified water is emulsified into the ointment.
 Exercise 2.1.27
Rp.
Argenti nitrici
Aq. purificatae
Ung. acidi borici 10%
0.5
0.5
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
Preparation procedure: Argentum nitricum is dissolved in the purified water and this solution
is emulsified into unguentum acidi borici 10%.
Eye ointments
Eye ointments are prepared according to different principles in the preparation of ointments.
The particular technological process is chosen depending on which form the drug is added
into the ointment (dissolved, suspended, emulsified). Emulsion eye ointments are the most
commonly prepared ointments in the pharmacy. The difference between them and other
107 products is the conditions under which they are prepared (see Basic requirements for the
preparation of liquid preparations - sterile preparations).
EXAMPLES
 Exercise 2.1.28
Rp.
Pilocarpini hydrochloridi
Aq. sterilisatae
Ung. ophthalmici simpl.
0.2
0.2
10.0
ad
M.f.ung.
D.S. Eye ointment in both eyes before sleeping.
Preparation procedure: Pilocarpinum hydrochloridum is dissolved in sterile water and this
solution is emulsified into the molten base with the same temperature.
 Exercise 2.1.29
Rp.
Dexamethasoni
Propylenglycoli
Ung. ophthalmici simpl.
0.01
0.1
10.0
ad
M.f.ung.
D.S. Eye ointment in both eyes before sleeping.
Preparation procedure: Trituration of dexamethasone in propyleglycole is emulsified into the
molten base with the same temperature (calculate amount of dexamethasone trituration).
Hydrophilic ointments are prepared from liquid and solid polyethylene glycol melted at
approximately 70C and stirred until cool. When preparing the solution ointments, thermostable drugs are added directly into the melt base, heat-labile drugs are added into semi-cooled
ointment base. When preparing suspension ointments, comminuted solids are premixed with a
melted polyethylene glycol ointment, a liquid polyethylene glycol may be used. The
preparation of an emulsion hydrophilic ointment is the same as for hydrophobic emulsion
ointments.
108 EXAMPLES
Hydrophilic ointments
 Exercise 2.1.30
Macrogoli unguentum
Macrogolum 300
Macrogolum 1500
25.0
25.0
Both types of polyethylene glycols are melted at a temperature of about 70C and the mixture
is stirred until cool. If the consistency of the prepared ointments is not suitable (consistency of
white Vaseline), it is allowable to change the prescribed amount of polyethylene glycol by up
to 10%.
Storage: Protect from light.
 Exercise 2.1.31
Rp.
Camphorae
Ung. macrogoli
1.0
50.0
ad
M. f. ung.
D. S. apply ointment to the skin
 Exercise 2.1.32
Rp.
Methylis salicylatis
Mentholi
Eucalypti etherolei
Ung. macrogoli
ad
0.75
1.0
0.25
50.0
M. f. ung.
D. S. apply ointment to the skin
109 2.2
Creams
 Hydrophobic cream bases without drugs
To prepare oleo-creams, an emulsifying base containing emulsifiers w/o is usually used. A
mixture of all prescribed hydrophilic liquids is added to a melted mixture of prescribed
hydrophobic substances with emulsifiers, eventually to emulsifying bases available on the
market (e.g. cetyl alcohol ointment), and both phases should be the same temperature (usually
50-80C) and stirred until cool. When preparing oleo-cream base for storage, the cream must
be stirred again after 24 hours.
Pharmacopoeal creams: Adeps lanae cum aqua, Alcoholis cetylici cremor, Alcoholum adipis
lanae cremor, Cremor refrigerans.
EXAMPLES
Pharmacopoeal formulas
 Exercise 2.2.1
Adeps lanae cum aqua
Adeps lanae
Aqua purificata
75.0
25.0
Preparation procedure: Water at the same temperature as the base is added to the melted adeps
lanae and stirred until cool.
Storage: At 25C or lower.
 Exercise 2.2.2
Alcoholis cetylici cremor
Alcoholis cetylici unguentum
Aqua purificata
30.0
20.0
Preparation procedure: Water at the same temperature as the base is added to the melted cetyl
alcohol ointment and stirred until cool.
Storage: Protect from light and freezing temperatures.
110  Exercise 2.2.3
Alcoholum adipis lanae cremor
Alcoholum adipis lanae unguentum
Aqua purificata
25.0
25.0
Preparation procedure: Water with the same temperature as the base is added to the melted
ointment from wool grease alcohol and stirred until cool.
Storage: Protect from light and freezing temperatures.
 Exercise 2.2.4
Cremor refrigerans
Cera alba
Cetylis palmitas
Helianthi oleum raffinatum
Natrii laurylsulfas
Aqua purificata
Ricini oleum virginale
Methylparabenum
Propylparabenum
Propylis gallatis
Geranii etheroleum
4.0
5.0
28.5
0.05
10.0
2.5
0.02
0.005
0.01
0.15 ml
Preparation procedure: White wax, cetyl palmitate, sunflower oil, sodium lauryl sulphate and
castor oil are melted over a water bath. Propyl gallate is dissolved into the melted mixture.
Parabens are dissolved in the water at the same temperature (about 50  C) and then are
admixed gradually into the melted base, then is stirred until cool. Finally, geranium essential
oil is added to the cooled cream.
Storage: Protect from light and freezing temperatures.
Labeling: Display antimicrobial agents on the label!
111 Exercise 2.2.5
Rp.
Cerae albae
Cetacei
Glyceroli monostearatis
Helianthi olei
Ricini olei
Propylis gallatis
Aq. purificatae
Mehylparabeni
Propylparabeni
Geranii etherolei
5.0
5.0
2.5
25.0
2.5
0.01
10.0
0.035
0.015
III guttae
M. f. cremor
D. S. apply cream to the skin
Preparation procedure: White wax, cetyl palmitate, glycerol monostearas, sunflower oil, and
castor oil are melted over a water bath. Propyl gallate is dissolved into the melted mixture.
Parabens are dissolved in the water at the same temperature (about 50  C) and then are
admixed gradually into the melted base, then is stirred until cool. Finally, geranium essential
oil is added to the cooled cream.
 Exercise 2.2.6
Rp.
Cerae albae
Cetacei
Adipis lanae aa
Helianthi olei
Cholesteroli
Natrii tetraboratis
Aq. purificatae
3.75
20.0
0.75
0.225
17.75
M. f. cremor
D. S. apply cream to the skin
112 Preparation procedure: White wax, cetaceum, adeps lanae, sunflower oil and cholesterol are
melted over a water bath. Then, sodium tetraborate dissolved in warm water is added while
stirring slowly.
 Exercise 2.2.7
Unguentum leniens
Cera alba
Cetaceum
Helianthi oleum
Ricini oleum
Natrii tetraboras
Aq. purificata
Geranii etherolei
4.0
7.5
25.0
5.0
0.25
8.25
III guttae
Preparation procedure: White wax, cetaceum, sunflower oil and castor oil are melted over a
water bath. The mixture is allowed to stay in the mortar without stirring until cool. The stiff
base is spread to the foam with light pressure. Then, sodium tetraborate dissolved in warm
water is added while stirring slowly. Finally, geranium essential oil is added to the cooled
cream.
 Hydrocream bases without drugs
Hydrocreams are distinguished according to the presence of emulsifiers:
 Stearin hydrocreams – are stabilized by an ionic emulsifier (soap), which is result of
in situ neutralization of stearin by an excess of the appropriate alkali (hydroxide or
carbonate sodium, potassium, ammonium, trolamine), usually by heating over a water
bath.
 Hydrocreams stabilized by a complex emulsifier – are stabilized by a combination
of emulsifiers o/w or w/o in the appropriate ratio, which are designated complex
emulsifiers. Usually, they are prepared at a temperature of 65-80 C by English (wet
gum) or Continental (dry gum) technique. English technique is used when the
individual emulsifiers are available: the emulsifier w/o is heated with other
hydrophobic components over a water bath until completely melted, forming a
homogeneous mixture. A solution of the emulsifier o/w is prepared in another vessel
113 with hydrophilic components. These two phases are then mixed together, stirred until
the cream has cooled while continuously scraping the mixture from the walls of the
mortar. The Continental technique is used when a mixture of emulsifiers (w/o and
o/w) are available. The mixture of emulsifiers is heated with hydrophobic substances,
and then the water phase at the same temperature is added gradually and stirred until
cool.
Pharmacopoeal ointments: Cremor anionicus, Cremor nonionicus.
EXAMPLES
Pharmacopoeal formulas
 Exercise 2.2.8
Cremor nonionicus
Unguentum emulsificans nonionicum
Propylenglycolum
Aqua purificata
Methylparabenum
Propylparabenum
20.0
5.0
25.0
0.05
0.025
Preparation procedure: A warm solution of parabens in a mixture of propylene glycol and
purified water at the same temperature is added to the nonionic emulsifying ointment melted
over a water bath at 70C and stirred until cool. Purified water is admixed to the cold cream to
100g.
Storage: Protect from light and freezing temperatures.
Labeling: Display antimicrobial agents on the label!
114  Exercise 2.2.9
Rp.
Kalii carbonatis
Cetacei
Stearini
Glyceroli 85%
Aq. conservantis
Lavandulae etherolei
0.5
1.0
6.25
10.0
32.2
0.05
M. f. cremor
D. S. Hand cream
Preparation procedure: Potassium carbonate is dissolved in a beaker in water with
preservatives; glycerol is then added and heated until boiling. An aqueous solution is added to
the melted cetaceum and stearin while continuously stirring. The mixture is kept over a
boiling water bath for approximately 30 min. while continuously adding evaporated water.
After removing the mixture from the water bath evaporated water is again added and the
mixture is vigorously stirred until cool (do not cool down quickly due to the creation of grainy
cream).
 Exercise 2.2.10
Rp.
Neoaquasorbi
Glyceroli 85%
Aq. conservantis
25.0
5.0
20.0
M. f. cremor
D. S. apply cream to the skin
Preparation procedure: Neoaquasob, glycerol and purified water are melted over water bath.
Cream is then stirred until it has cooled, with continuous scraping of the mixture from the
walls of the mortar.
115  Exercise 2.2.11
Rp.
Stearini
Adipis lanae
Paraffini liquidi
Trolamini
Glyceroli 85%
Aq. purificatae
7.5
1.0
12.5
1.0
2.5
50.0
ad
M. f. cremor
D. S. apply cream on the skin
Preparation procedure: Stearin, adeps lanae and liquid paraffine are melted over a water bath.
Trolamin, glycerol and water are heated up in the beaker with the same temperature as the
cream base. Both phases are then mixed together at the same temperature and stirred until
cool, with continuous scraping of the mixture from the walls of the mortar.
 Oleocreams and hydrocreams with drugs
Two-phase cream – the drug is dissolved in the phase that is soluble, then is continued as in
the preparation of the corresponding type of cream. Liquid drugs that are miscible with the
outer phase of the cream can be stirred into the finished cream. Volatile substances are then
added to the cold cream.
Three-phase cream - contains drugs that are insoluble in any phase of the cream. The
comminuted drug or mixture of drugs is premixed with the part of the cream base or the liquid
that is miscible with the outer phase of the cream, and then the rest of the cream is added. In
the preparation of three-phase oleocream containing less of the aqueous phase (up to 20%) at
room temperature (e.g. hydrophobic base Synderman allows for emulsification at room
temperature) it is possible to apply the principles of three-phase hydrophobic ointment
preparation, i.e., the hydrophobic suspension ointment is prepared in which the prescribed
amount of hydrophilic liquid is emulgated.
Pharmacopoeal ointments: Aluminii acetotartratis cremor.
116 EXAMPLES
Pharmacopoeal formulas
 Exercise 2.2.12
Aluminii acetotartratis cremor
Aluminii acetotartratis solutio
Aqua purificata
Adeps lanae
Vaselinum flavum
5.0
5.0
10.0
30.0
Preparation procedure: Adeps lanae and yellow Vaseline is heated over a water bath at 40C
and homogenized. The mixture of aluminii acetotartratis solution and purified water (40C) is
then mixed gradually into the melted base. The mixture is then stirred until cool. After 24
hours the ointment is re-mixed.
Storage: Protect from light and freezing temperatures.
EXAMPLES
 Exercise 2.2.13
Rp.
Geranii etherolei
Adipis lanae cum aq.
Acidi borici sol. 3%
Helianthi olei
Syndermani
ad
1.0
1.5
12.5
12.5
50.0
M. f. cremor
D. S. apply cream to the skin
Preparation procedure: Adeps lanae cum aqua, sunflower oil and synderman are melted over a
water bath. Then, solution of boric acid heated to the same temperature as the base is added to
the base and stirred until cool with continuous scraping of the mixture from the walls of the
mortar. Finally, geranium essential oil is added to the cooled cream.
117  Exercise 2.2.14
Rp.
Acidi salicylici
Aq. purificatae
Neoaquasorbi
ad
1.0
19.0
50.0
M. f. cremor
D. S. apply cream to the skin
Preparation procedure: Neoaquasor is mixed with purified water over water bath. Salicylic
acid is then suspended into the base.
118 2.3
Gels
Gels are prepared due to the swelling of the polymers. Preparation is not uniform, since
different substances require different conditions for swelling, dissolution and gelation (sol-gel
transition). Generally, they are prepared by layering finely-powdered gelling agents on a
liquid surface at room temperature. For substances that can very easily form clumps, which
makes swelling difficult, it is sometimes recommended to premix the gelling agents with
alcohol or glycerol.
Methods of preparation
1. Gels prepared at room temperature - from tragacanth, methyl cellulose, povidone,
etc.
2. Gels prepared at higher temperature - agar, starch, gelatin, sodium salt of carmellose
3. Gels prepared by neutralization (change pH) - polyacrylic acid (carbomers).
Pharmacopoeal gels: Glyceroli unguentum, Zinci oxidi gelatina mollis.
EXAMPLES
Pharmacopoeal formulas
 Exercise 2.3.1
Zinci oxidi gelatina mollis
Zinci oxidum (125)
Glycerolum 85%
Gelatina
Aqua conservans
10.0
40.0
15.0
35.0
Preparation procedure: Gelatin is uniformly wetted by water with preservatives and is
allowed to swell for 15 minutes. The mixture is then heated over a water bath at a temperature
not exceeding 65C until the gelatin dissolves. The evaporated water is replaced by warm
purified water and the comminuted mixture of zinc oxide is mixed into the gelatin solution
with 85% glycerol. The warm mixture is then poured into a wide-necked bottle.
119 Labeling: Display antimicrobial agents on the label!
 Exercise 2.3.2
Glyceroli unguentum
Glycerolum 85%
Methylparabenum
Ethanolum 96% (V/V)
Tritici amylum (125)
Aqua purificata
90.0
0.2
1.0
10.0
15.0
Preparation procedure: The modified procedure - glycerol is heated to approximately 90°C.
Wheat starch is then mixed with water and a methylparaben solution in alcohol. The mixture
is then heated over a water bath, while constantly being stirred until the mixture thickens homogeneous translucent ointment is then created. The evaporated water is refilled and stirred
until cool.
Storage: Protect from light.
Labeling: Display antimicrobial agents on the label!
Examples of formulas
 Exercise 2.3.3
Rp.
Carbopoli
Natrii hydroxidi sol.10%
Sol. methylthionii chloridi 1%
Aq. purificatae
ad
0.25
q.s.
1 gtt I
50.0
M. f. gel
D. S. Lubricant
120  Exercise 2.3.4
Rp.
Urae
Carbopoli
Glyceroli 85%
Trolamini
Aq. purificatae
2.5
0.25
5.0
q.s.
50.0
ad
M. f. gel
D. S. Urea gel
Preparation procedure: Note for tasks 3 and 4: the gel is prepared by layering Carbopol at
approximately half the amount on the surface of the water (in the mortar), and after the
swelling it is stirred to a smooth mixture. The gel is prepared by adding (neutralization) the
appropriate alkali drops. Then the remaining water (or the aqueous solution of the drugs and
other substances) is added to the mixture.
 Exercise 2.3.5
Gelatum gelatinae
Gelatina
Aq. conservans
10.0
90.0
Preparation procedure: Gelatin is added to the beaker with water with preservatives and is
allowed to swell for 15 minutes. By heating over a water bath (70 C) the gelatin is dissolved
(do not boil!!!). Evaporated water is added with hot purified water, and the solution is then
poured into a wide-necked bottle, closed and allowed to cool.
 Exercise 2.3.6
Gelatum agari
Agarum
Aq. conservans
1.0
99.0
Preparation procedure: Agar with preservative water (without swelling) is heated on the
cooker to a boil and is boiled until agar is dissolved. Evaporated water is added with the hot
121 purified water, and then the solution is poured into a wide-necked bottle, closed and allowed
to cool.
122 2.4
Pastes
Pastes are prepared according to the same principles as suspension or three-phase ointments,
the difference being that the hydrophobic base is completely melted for easy preparation.
When a cream base is used for preparing paste, especially hydrophilic cream (e.g.
Ambiderman), it is used from premixing of the solids.
Pharmacopoeal pasta: Sulfuris pasta 50%, Sulfuris pasta composita, Zinci oxidi pasta, Zinci
oxidi pasta 50%, Zinci oxidi pasta salicylata.
Examples of pharmacopoeal formulas
 Exercise 2.4.1
Sulfuris pasta composita
Sulfur ad usum externum
Kalii carbonas
Sapo kalinus
Vaselinum flavum
20.0
10.0
15.0
55.0
Sulphur for external use and potassium carbonate are mixed together. The mixture is first
mixed with potassium soap (sapo kalinus), and then is gradually admixed to the melted
Vaseline.
Storage: Protect from light.
 Exercise 2.4.2
Zinci oxidi pasta
Zinci oxidum (125)
Tritici amylum (125)
Vaselinum flavum
25.0
25.0
50.0
Preparation procedure: A mixture of dried zinc oxide and wheat starch are strained through a
sieve, and are thoroughly comminuted in a warm stainless steel mortar with melted yellow
Vaseline and then mixed until cool.
Storage: Protect from light.
123  Exercise 2.4.3
Zinci oxidi pasta mollis
Zinci oxidum (125)
Helianthi oleum raffinatum
Alcoholes adipis lanae
Vaselinum flavum
30.0
20.0
5.0
45.0
Preparation procedure: Zinc oxide is thoroughly comminuted with sunflower oil. The melted
mixture of alcohols adipis lanae and yellow Vaseline is gradually admixed to the obtained
suspension , and stirred until cool.
Storage: Protect from light.
 Exercise 2.4.4
Zinci oxidi pasta salicylata
Acidum salicylicum (90)
Vaselinum flavum
Zinci oxidi pasta
Preparation procedure:
2.0
2.0
96.0
Salicylic acid is thoroughly comminuted with melted yellow
Vaseline, and is gradually admixed into zinc paste.
Storage: Protect from light.
Examples of formulas:
 Exercise 2.4.5
Rp.
Bismuthi subgallatis
Zinci oxidi
Tritici amyli
Helianthi olei
Adipis lanae cum aq.
17.0
20.0
20.0
18.0
25.0
M. f. pasta
D. S. Schmiden pasta
124 Preparation procedure: Bismuth subgallas, zinc oxide and wheat starch are premixed with
sunflower oil. Adeps lanae cum aqua is melted over water bath, gradually admixed to the
obtained suspension, and stirred until cool.
 Exercise 2.4.6
Rp.
Picis lithantracis
Zinci oxidi
Talci
Cremoris Neoaquasorbi
1.5
aa
ad
15.0
100.0
M. f. pasta
D. S. apply pasta to the skin
Preparation procedure: Pix is dissolved in about 5g of ether. Dissolved pix is then mixed with
powders of zinc oxide and talc. Finally, Neoaquasorb cream is gradually admixed to the
mixture.
125 Autors:
Kateřina Dvořáčková
Aleš Franc
Jan Gajdziok
Martina Kejdušová
David Vetchý
Title:
MEDICAL PHORMS AND BIOPHARMACY
I.Liquid and semi-solid drugs
Department:
Department of Pharmaceutics
Pages:
125
Edition:
1st
Publisher:
University of Veterinary and Pharmaceutical Sciences Brno
ISBN 978-80-7305-671-1