Microencapsulation - International Journal of Pharma and Bio

ISSN 0975-6299
Vol 3/Issue 1/Jan – Mar 2012
International Journal of Pharma and Bio Sciences
PHARMACEUTICS
REVIEW ARTICLE
MICROENCAPSULATION: A REVIEW
JYOTHI SRI.S* 1, A.SEETHADEVI 1, K.SURIA PRABHA 1, P.MUTHUPRASANNA
1
AND ,P.PAVITRA2
1
2
Department Of Pharmaceutics, Hindu College Of pharmacy, Guntur, INDIA.
Department Of Pharmaceutics, Shri Vishnu College Of pharmacy, Bhimavaram, INDIA
JYOTHI SRI.S
Department Of Pharmaceutics, Hindu College Of pharmacy, Guntur, INDIA.
ABSTRACT
Microencapsulation is the process of surrounding or enveloping one substance
within another substance on a very small scale, yielding capsules ranging from less than
one micron to several hundred microns in size. The encapsulation efficiency of the
microparticles or microsphere or microcapsule depends upon different factors like
concentration of the polymer, solubility of polymer in solvent, rate of solvent removal,
solubility of organic solvent in water etc. Microencapsulation may be achieved by a myriad
of techniques. Substances may be microencapsulated with the intention that the core
material be confined within capsule walls for a specific period of time. Alternatively, core
materials may be encapsulated so that the core material will be released either gradually
through the capsule walls, known as controlled release or diffusion, or when external
conditions trigger the capsule walls to rupture, melt, or dissolve. This article is a review of
microencapsulation and materials involved in it, morphology of microcapsules,
microencapsulation technologies, purposes of microencapsulation, and benefits of
microencapsulation, release mechanisms, and application fields, with special emphasis on
microencapsulated additives in building construction materials.
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KEYWORDS
Microencapsulation, morphology, release mechanism, benefits,technologies, applications
INTRODUCTION
Micro-encapsulation is a process in
which tiny particles or droplets are surrounded
by a coating to give small capsules. In a
relatively simplistic form, a microcapsule is a
small sphere with a uniform wall around it. The
material inside the microcapsule is referred to as
the core, internal phase, or fill, whereas the wall
is sometimes called a shell, coating, or
membrane. Most microcapsules have diameters
between a few micrometers and a few
millimeters.
The definition has been expanded, and
includes more foods. Every class of food
ingredient has been encapsulated; flavors are
the most common. The technique of
microencapsulation depends on the physical and
chemical properties of the material to be
encapsulated.1 These micro-capsules have a
number of benefits such as converting liquids to
solids, separating reactive compounds, providing
environmental protection, improved material
handling properties. Active materials are then
encapsulated in micron-sized capsules of barrier
polymers (gelatin, plastic, wax ...).2 Many
microcapsules however bear little resemblance
to these simple spheres. The core may be a
crystal, a jagged adsorbent particle, an emulsion,
a suspension of solids, or a suspension of
smaller microcapsules. The microcapsule even
may have multiple walls.
MATERIALS
INVOLVED
MICROENCAPSULATION:
IN
Microencapsulation is the process by
which individual particles or droplets of solid or
liquid material (the core) are surrounded or
coated with a continuous film of polymeric
material (the shell) to produce capsules in the
micrometer to millimeter range, known as
microcapsules.(Fig.No.1)
Figure No.1
Microcapsule with core and coat
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Core Material:
The material to be coated
It may be liquid or solid
Liquid core may be dissolved or dispersed
material
Composition of coating material:
Drug or active constituent
Additive like diluents
Stabilizers
Release rate enhancers
E.g. Coating materials:
•
G
 ums: Gum arabic, sodium alginate,
carragenan
•
C
 arbohydrates: Starch, dextran, sucrose
•
Celluloses: Carboxymethylcellulose,
methycellulose.
•
L
 ipids: Bees wax, stearic acid,
phospholipids.
•
P
 roteins: Gelatin, albumin.
Coating Material:
Inert substance which coats on core with
desired thickness
Compatible with the core material
Stabilization of core material.
Inert toward active ingredients.
Controlled release under specific conditions.
The coating can be flexible, brittle, hard, thin
etc.
Abundantly and cheaply available
Composition of coating
• Inert polymer
• Plasticizer
• Colouring agent
MORPHOLOGY OF MICROCAPSULES:
The morphology of microcapsules depends
mainly on the core material and the deposition
process of the shell.
1- Mononuclear (core-shell) microcapsules
contain the shell around the core.
2- Polynuclear capsules have many cores
enclosed within the shell.
3- Matrix encapsulation in which the core
material is distributed homogeneously into the
shell material.
- In addition to these three basic morphologies,
microcapsules can also be mononuclear with
multiple shells, or they may form clusters of
microcapsules. (Fig.No.2)
Figure. No 2
Morphology of Microcapsules
REASON FOR MICROENCAPSULATION AND
RELEASE MECHANISM:
The reasons for microencapsulation are
countless. In some cases, the core must be
isolated from its surroundings, as in isolating
vitamins from the deteriorating effects of oxygen,
retarding evaporation of a volatile core,
improving the handling properties of a sticky
material, or isolating a reactive core from
chemical attack. In other cases, the objective is
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not to isolate the core completely but to control
the rate at which it leaves the microcapsule, as
in the controlled release of drugs or pesticides.
The problem may be as simple as masking the
taste or odor of the core, or as complex as
increasing the selectivity of an adsorption or
extraction
process.
The
reasons
for
microencapsulation are also described by John
Franjione, Ph.D., and Niraj Vasishtha, PhD: as
"Microencapsulation is like the work of a clothing
designer. He selects the pattern, cuts the cloth,
and sews the garment in due consideration of
the desires and age of his customer, plus the
locale and climate where the garment is to be
worn. By analogy, in microencapsulation,
capsules are designed and prepared to meet all
the requirements in due consideration of the
properties of the core material, intended use of
the product, and the environment of storage"
Different purposes of microcapsule-based
final products require different characteristics of
microcapsules. The size and shape of
microcapsules,
chemical
properties
of
microcapsule walls, and their degradability,
biocompatibility and permeability have to be
considered in the selection of raw materials and
microencapsulation processes. The purpose of
microencapsulation is usually defined by the
permeability. Microcapsules with impermeable
walls are used in products where isolation of
active substances is needed, followed by a quick
release under defined conditions. The effects
achieved with impermeable microcapsules
include: separation of reactive components,
protection of sensitive substances against
environmental effects, reduced volatility of highly
volatile substances, conversion of liquid
ingredients into a solid state, taste and odour
masking, and toxicity reduction. On the other
hand, microcapsules with permeable walls
enable prolonged release of active components
into the environment, such as in the case of
prolonged release drugs, perfumes, deodorants,
repellents, etc., or immobilization with locally
limited
activity
of
microencapsulated
substances.
Examples
of
later
include
microencapsulated fertilizers and pesticides with
locally limited release to reduce leaching into the
ground water, or microencapsulated catalysts
and enzymes for chemical and biotechnological
processes.(3)
The
mechanisms
of
releasing
encapsulated materials are planned in advance
and
depend
on
the
purpose
of
microencapsulation. An analysis of several
hundred patent documents revealed that the first
developed and still often used is the mechanism
of external pressure which breaks the
microcapsule wall and releases the liquid from
the core. This principle is applied in pressuresensitive copying papers (pressure of the penball or typewriter head), multi-component
adhesives (activation in a press), deodorants
and fungicides for shoes (mechanical pressure
caused by walking), polishing pastes (rubbing)
and aromas and sweeteners in chewing gums
(chewing).
In
some
applications,
the
microcapsule wall breaks because of inner
pressure, e.g. for blowing agents in the
production of light plastic materials and synthetic
leather. In instant drinks, microcapsules
dissolve in water.(4) Dissolution at the selected
pH value is useful for microencapsulated
catalysts and pharmaceuticals. Drugs, vitamins,
minerals, essential amino acids, fatty acids, or
even whole diets, can be released into the
gastro-intestinal tract by enzymatic degradation
of digestible microcapsules. The core substance
can be released by abrasion of the
microcapsule wall, e.g. in antistatic and
fragrances for textiles (abrasion in washing
machines and dryers), or for grinding and cutting
additives. In many applications, core materials
are released by heat. Heat-sensitive recording
papers (e.g. telefax paper), temperature
indicators for frozen food, heat-sensitive
adhesives, textile softeners and fragrances in
formulations for dryers, cosmetic components to
be released at body temperature and aromas for
tea and baking, are based on the effect of
melting
of
the
microcapsule
wall.
Microencapsulated
fire
retardants
or
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extinguishers, based on release caused by
burning of microcapsule walls, are used in fireproof materials. These types of microcapsules
are used for wall paper, carpets, curtains, fireprotecting clothes, and added to plastics and
coatings for electric devices and wires.
Microcapsules
in
special
photographic
emulsions, light-sensitive papers and toners for
photocopiers are decomposed (or hardened) by
light. If the wall is permeable, it slowly
releases the content of the core. This
mechanism can be applied in controlled drug
release
products,
aromas,
fragrances,
insecticides and fertilizers. In the case of
microencapsulated cells and enzymes in
biotechnology,
high-molecular
weight
components can be retained in microcapsules,
while low-molecular by-products and substrate
residues
are
extracted
through
semipermeable microcapsule walls. A special
example is that of microencapsulated phase
change materials for active accumulation and
release of heat in textiles, shoes and building
insulation materials. To remain functional over
numerous phase transition cycles, they have to
remain encapsulated within the impermeable
and mechanically resistant microcapsule wall for
the whole product life.
BENEFITS OF MICROENCAPSULATION:
1Microorganism
and
enzyme
immobilization.
- Enzymes have been encapsulated in cheeses
to accelerate ripening and flavor development.
The encapsulated enzymes are protected from
low pH and high ionic strength in the cheese.
• The encapsulation of microorganisms has been
used to improve stability of starter cultures.
2-Protection against UV, heat, oxidation,
acids, bases (e.g. colorant sand vitamins).
E.g. Vitamin A / monosodium glutamate
4- Masking of taste or odours.
5- Improved processing, texture and less
wastage of ingredients.
• Control of hygroscopy
• enhance flowability and dispersibility
• dust free powder
• enhance solubility
6-Handling liquids as solids
7-There is a growing demands for nutritious
foods for children which provides them with
much needed vitamins and minerals during the
growing age. Microencapsulation could deliver
the much needed ingredients in children friendly
and tasty way.
8- Enhance visual aspect and marketing
concept.
9-Today's textile industry makes use of
microencapsulated materials to enhance the
properties of finished goods. One application
increasingly utilized is the incorporation of
microencapsulated phase change materials
(PCMs).
Phase change materials absorb and release
heat in response to changes in environmental
temperatures. When temperatures rise, the
phase change material melts, absorbing excess
heat, and feels cool. Conversely, as
temperatures fall, the PCM releases heat as it
solidifies, and feels warm.
10- Pesticides are encapsulated to be
released overtime, allowing farmers to apply
the pesticides less amounts than requiring very
highly concentrated and toxic initial applications
followed by repeated applications to combat the
loss of efficacy due to leaching, evaporation, and
degradation.
3- Improved shelf life due to preventing
degradative reactions (dehydration, oxidation).
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11- Ingredients in foods are encapsulated for
several reasons.
12- Controlled and targeted release of active
• Most flavorings are volatile; therefore ingredients.
encapsulations of these components
• Many varieties of both oral and
extend the shelf-life of these products.
injected pharmaceutical formulations
are microencapsulated to release over
• Some ingredients are encapsulated to
longer periods of time or at certain
mask taste, such as nutrients added to
locations in the body.
fortify a product without compromising
the product’s intended taste.
• Alternatively, flavors are sometimes 13- Microencapsulation allows mixing of
incompatible compounds.
encapsulated to last longer, as in
chewing gum.
Figure .No.3
MICROENCAPSULATION TECHNOLOGIES
Microencapsulation processes are usually
categorized into two groupings: chemical
processes5-10 and mechanical or physical
processes. These labels can, however, be
somewhat misleading, as some processes
classified as mechanical might involve or even
rely upon a chemical reaction, and some
chemical techniques rely solely on physical
events. A clearer indication as to which category
an encapsulation method belongs is whether or
not the capsules are produced in a tank or
reactor containing liquid, as in chemical
processes, as opposed to mechanical or
physical processes, which employ a gas phase
as part of the encapsulation and rely chiefly on
commercially available devices and equipment to
generate microcapsules. There are various
techniques available for the encapsulation of
core materials.11,12,13 and microencapsulation
processes with their relative particle size ranges
is mentioned in (Table.No.1)
Table.No.1
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Microencapsulation Processes with Their Relative Particle Size Ranges
PHYSICO - CHEMICAL
PROCESSES
Coacervation (2 – 1200 um)
PHYSICO - MECHANICAL
PROCESSES
Spray-drying (5 – 5000 um)
Polymer-polymer incompatibility
(0.5 – 1000 um)
Solvent evaporation
(0.5 – 1000 um)
Encapsulation by supercritical
Fluid
Encapsulation by Polyelectrolyte
multilayer (0.02 – 20 um)
Phase Inversion (0.5—5.0 um)
Fluidized- bed technology
(20 – 1500 um)
Pan coating (600 – 5000 um)
Hot Melt (1—1000 um)
I.
PHYSICO CHEMICAL PROCESSES
1. COESERVATION PHASE SEPARATION:
A coacervate is a tiny spherical droplet of
assorted organic molecules (specifically, lipid
molecules) which is held together by
hydrophobic forces from a surrounding liquid.
Coacervates measure 1 to 100 micrometers
across, possess osmotic properties and form
spontaneously from certain dilute organic
solutions. Their name derives from the Latin
coacervare, meaning to assemble together or
cluster. They were even once suggested to
have played a significant role in the evolution of
cells and, therefore, of life itself.
Formation
In water, organic chemicals do not necessarily
remain uniformly dispersed but may separate
out into layers or droplets. If the droplets which
form contain a colloid, rich in organic
compounds and are surrounded by a tight skin
of water molecules, then they are known as
Coacervates. These structures were first
investigated by the Dutch chemist H.G.
Bungenberg de Jong, in 1932. A wide variety of
solutions can give rise to them; for example,
Spinning disc (5 – 1500 um)
Co-extrusion
(250 – 2500 um)
Interfacial polymerization
(0.5 – 1000 um)
In situ polymerization
(0.5 – 1100 um)
Coacervates form spontaneously when a
protein, such as gelatin, reacts with gum Arabic.
They are interesting not only in that they provide
a locally segregated environment but also in
that their boundaries allow the selective
absorption of simple organic molecules from the
surrounding medium. In Oparin's view this
amounts to an elementary form of metabolism.
Bernal commented that they are "the nearest
we can come to cells without introducing any
biological – or, at any rate, any living biological
– substance." However, the lack of any
mechanism by which Coacervates can
reproduce leaves them far short of being living
systems.14
Two methods for coacervation are available,
namely simple and complex processes.
• In simple coacervation, a desolvation
agent is added for phase separation.
• Whereas complex coacervation involves
complexation between two oppositely
charged polymers.
Complex coacervation
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Complex coacervation refers to the phase
separation of a liquid precipitate, or phase,
when solutions of two hydrophilic colloids are
mixed under suitable conditions. The general
outline of the processes consists of three steps
carried under continuous agitation [15]:
Step 1: Formation of three immiscible
chemical phases
The immiscible chemical phases are (i) a liquid
manufacturing vehicle phase (ii) a core material
phase
and
(iii)
a
coating
material
phase.(Fig.No.4) To form the three phases, the
core material is dispersed in a solution of the
coating polymer, the solvent for the polymer
being the liquid manufacturing vehicle phase.
The coating material phase, an immiscible
polymer in a liquid state, is formed by utilizing
one of the methods of phase separation
coacervation, that is,
•
By changing the temperature of the
polymer solution
•
By adding a salt
•
By adding a non-solvent
•
By adding incompatible polymer to the
polymer solution
•
By
inducing
a
polymer-polymer
interaction.
Figure .No.4
Process of Coacervation:
Step 2: Depositing the liquid polymer coating
upon the core material
This is accomplished by controlled, physical
mixing of the coating material (while liquid) and
the core material in the manufacturing vehicle.
Deposition of the liquid polymer coating around
the core material occurs if the polymer is
adsorbed at the interface formed between the
core material and the liquid vehicle phase, and
this adsorption phenomenon is a prerequisite to
effective coating. The continued deposition of the
coating material is promoted by a reduction in
the total free interfacial energy of the system,
brought about by the decrease of the coating
material surface area during coalescence of the
liquid polymer droplets.
Step 3: Rigidizing the coating
This is usually done by thermal, cross linking or
desolvation techniques, to form a self sustaining
microcapsule.
Complex coacervation can also occur
with the neutralization of two oppositely
charged polymers. The core material such as
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an oily phase is dispersed in an aqueous
solution of the two polymers. A change is
made in the aqueous phase (pH) to induce
the formation of a polymer rich phase that
becomes the wall material. The Coacervates
are usually stabilized by thermal treatment,
crosslinking
or
desolvation
techniques.(Fig.No.5),They found that the
yield
of
gelatin–acacia
microcapsules
decreases at surfactant concentrations above
or below the optimum. Inhibition of
coacervation due to high concentrations of
surfactants
and
disturbance
of
microencapsulation due to high hydrophilic–
lipophilic balance (HLB) values have been
reported. In general, the concentration of a
surfactant required to increase the yield of
microcapsules is too low to produce regularsized droplets. The analysis of the size
distribution shows that the microcapsules are
multi-dispersed. In the coacervation process,
the pH value of a continuous gelatin phase
would be adjusted above its isoelectric point
to form negatively charged gelatin, which is
able to create monodispersed droplets. The
positively charged gelatin is attracted to the
negatively charged acacia to form coacervate
droplets when the pH value is adjusted to
below its isoelectric point. Therefore, the
particle size distributions of emulsion droplets
are effected by the factors of pH adjustment,
especially the adding rate of the acidifying
agent. The report shows the indomethacin
microcapsules had the slowest release rate
when the coacervation pH was adjusted to the
electrical equivalence pH value and not to the
pH of maximum coacervate yield. Gelatin is
only stable at the pH value between 4 and 6,
our data shown that the alkalization caused
the breaking of the wall of the microcapsule
made by the crosslinking agent of glycerol.
Not only is the purple-colored shikonin
alkalized into a blue color, but the
saponification effects may also be undergone
by the solvent (sesame oil) of extract
containing shikonin reacting with sodium
hydride. However, this reaction would not be
shown in the microcapsule made by the
crosslinking agent of formaldehyde. This
explains why the shell of the microcapsule
made by formaldehyde is more rigid than that
made by glycerol. In other words, the
microcapsule made by glycerol has a more
permeable shell than made by formaldehyde.
The particle size of the microcapsule was not
affected by the difference of crosslinking
agents. Using the low concentration 3% and
6% of plasticizer glycerol instead of
formaldehyde, similar morphology results
were obtained. Increasing the amount of
crosslinking agent leads to an increase in the
encapsulation ability. However, the results
indicated that above 6% of glycerin,
encapsulation ability decreases as the
crosslinking agent increases due to the
alteration of the mechanism and inability to
integrate into the network even after the
addition of an excess amount.
Figure.No.5
Complex Coacervation
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2. POLYMER-POLYMER INCOMPATIBILITY :
( phase separation)
• This method utilizes two polymers that are
soluble in a common solvent; yet do not mix
with one another in the solution.
•
The polymers form two separate phases, one
rich in the polymer intended to form the
capsule walls, the other rich in the
incompatible polymer meant to induce the
separation of the two phases. The second
polymer is not intended to be part of the
finished microcapsule wall.(Fig.No.6)
Figure. No. 6
Polymer-Polymer Incompatibility
3. SOLVENT EVAPORATION:
Microencapsulation by solvent evaporation
technique is widely used in pharmaceutical
industries. It facilitates a controlled release of a
drug, which has many clinical benefits. Water
insoluble polymers are used as encapsulation
matrix using this technique. Biodegradable
polymer PLGA (poly (lactic-co-glycolic acid)) is
frequently used as encapsulation material.16
Different kinds of drugs have been successfully
encapsulated: for example hydrophobic drugs
such as cisplatin, lidocaine, naltrexone and
progesterone; and hydrophilic drugs such as
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solvents
like
dichloromethane
or
insulin, proteins, peptide and vaccine. The
chloroform with vigorous stirring to form
choice of encapsulation materials and the testing
the primary water in oil emulsion.
of the release of drug have been intensively
investigated.
However
process-engineering
•
This emulsion is then added to a large
aspects of this technique remain poorly reported.
volume of water containing an emulsifier
To succeed in the controlled manufacturing of
like PVA or PVP to form the multiple
microspheres, it is important to investigate the
emulsion (w/o/w).
latter.
•
The double emulsion is then subjected to
Process involved:
stirring until most of the organic solvent
•
Prepare an aqueous solution of the drug
evaporates, leaving solid microspheres.
(may contain a viscosity building or •
The microspheres can then be washed
stabilizing agent)
and dried.(Fig.No.7)
•
Then added to an organic phase
consisting of the polymer solution in
Figure .No. 7
Solvent Evaporation:
4. POLYMER ENCAPSULATION BY RAPID
EXPANSION OF SUPERCRITICAL FLUIDS:
- Supercritical fluids are highly compressed
gases that possess several properties of both
liquids and gases.
- The most widely used being supercritical CO2
and nitrous oxide (N2O).
-
-
A small change in temperature or pressure
causes a large change in the density of
supercritical fluids.
Supercritical CO2 is widely used for its low
critical temperature value, in addition to its
nontoxic, non flammable properties; it is also
readily available, highly pure and costeffective. This technology also applicable to
prepare nanoparticles also.(Fig.No.8)
Figure.No8.
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RAPID EXPANSION OF SUPERCRITICAL FLUIDS
Process Involved:
Supercritical fluid contains the active
ingredient and the shell material are
maintained at high pressure and then
released at atmospheric pressure through a
small nozzle.
The sudden drop in pressure causes
desolvation of the shell material, which is
then deposited around the active ingredient
(core) and forms a coating layer.
o Different core materials such as pesticides,
pigments, vitamins, flavors, and dyes are
encapsulated using this method.17,18,19
o A wide variety of shell materials e.g. paraffin
wax and polyethylene glycol are used for
encapsulating core substances.
o The disadvantage of this process is that both
the active ingredient and the shell material
must be very soluble in supercritical fluids.
5. HYDROGEL MICROSPHERES:
• Microspheres made of gel-type polymers,
such as alginate, are produced by dissolving
the polymer in an aqueous solution20
• Then, suspending the active ingredient in the
mixture
• Extruding through a precision device,
producing micro droplets
• Then fall into a hardening bath that is slowly
stirred. The hardening bath usually contains
calcium chloride solution.(Fig.No.9)
Advantage:
The method involves an “all-aqueous” system
and avoids residual solvents in microspheres.
The particle size of microspheres can be
controlled by:
o Using various size extruders or
o By varying the polymer solution flow rates.
Figure.No.9
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Hydrogel Microspheres
TYPE B: MECHANICAL PROCESS
SPRAY-DRYING & SPRAY-CONGEALING:
Microencapsulation by spray-drying is a
low-cost commercial process which is mostly
used for the encapsulation of fragrances, oils
and flavors. Spray drying is the continuous
transformation of feed from a fluid state into
dried particulate form by spraying the feed into a
hot drying medium. An emulsion is prepared by
dispersing the core material, usually an oil or
active ingredient immiscible with water; into a
concentrated solution of wall material until the
desired size of oil droplets are attained. The
resultant emulsion is atomized into a spray of
droplets by pumping the slurry through a rotating
disc into the heated compartment of a spray
drier. There the water portion of the emulsion is
evaporated, yielding dried capsules of variable
shape containing scattered drops of core
material. The capsules are collected through
continuous discharge from the spray drying
chamber.21This method can also be used to dry
small microencapsulated materials from aqueous
slurry that are produced by chemical methods. (
Fig. No. 10)
Figure .No.10
Spray-Drying
Spray congealing can be done by spray
drying equipment where protective coating will
be applied as a melt. Core material is dispersed
in a coating material melt rather than a coating
solution. Coating solidification is accomplished
by spraying the hot mixture into cool air stream.
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Waxes, fatty acids, and alcohols, polymers which
are solids at room temperature but meltable at
reasonable temperature are applicable to spray
congealing.22, prepared mucoadhesive micro
particles and to design an innovative vaginal
delivery systems for econazole nitrate (ECN) to
enhance the drug antifungal activity. Seven
different formulations were prepared by spraycongealing, a lipid-hydrophilic matrix (Gelucire
((R)) 53/10) was used as carrier and several
mucoadhesive polymers such as chitosan,
sodium carboxymethylcellulose and poloxamers
(Lutrol((R)) F68 and F127) were added.
FLUIDIZED-BED TECHNOLOGY:
Fluid bed coating, another mechanical
encapsulation
method,
is
restricted
to
encapsulation of solid core materials, including
liquids absorbed into porous solids. This
technique is used extensively to encapsulate
pharmaceuticals.
Solid
particles
to
be
encapsulated are suspended on a jet of air and
then covered by a spray of liquid coating
material.23 The capsules are then moved to an
area where their shells are solidified by cooling
or solvent vaporization. The process of
suspending, spraying, and cooling is repeated
until the capsules' walls are of the desired
thickness. This process is known as the Wurster
process when the spray nozzle is located at the
bottom of the fluidized bed of particles. Both
fluidized bed coating and the Wurster process
are variations of the pan coating method
The liquid coating is sprayed onto the
particles and the rapid evaporation helps in the
formation of an outer layer on the particles. The
thickness and formulations of the coating can be
obtained as desired. Different types of fluid-bed
coaters include top spray, bottom spray, and
tangential spray (Fig.11).
In the top spray system the coating
material is sprayed downwards on to the fluid
bed such that as the solid or porous particles
move to the coating region they become
encapsulated.
Increased
encapsulation
efficiency and the prevention of cluster formation
are achieved by opposing flows of the coating
materials and the particles. Dripping of the
coated particles depends on the formulation of
the coating material. Top spray fluid-bed coaters
produce higher yields of encapsulated particles
than either bottom or tangential sprays.
The bottom spray is also known as
“Wurster’s coater” in recognition of its
development by Prof. D.E. Wurster 24. This
technique uses a coating chamber that has a
cylindrical nozzle and a perforated bottom plate.
The cylindrical nozzle is used for spraying the
coating material. As the particles move upwards
through the perforated bottom plate and pass the
nozzle area, they are encapsulated by the
coating material. The coating material adheres to
the particle surface by evaporation of the solvent
or cooling of the encapsulated particle. This
process is continued until the desired thickness
and weight is obtained. Although it is a time
consuming process, the multilayer coating
procedure helps in reducing particle defects.
The tangential spray consists of a rotating
disc at the bottom of the coating chamber, with
the same diameter as the chamber. During the
process the disc is raised to create a gap
between the edge of the chamber and the disc.
The tangential nozzle is placed above the
rotating disc through which the coating material
is released. The particles move through the gap
into the spraying zone and are encapsulated. As
they travel a minimum distance there is a higher
yield of encapsulated particles.
Figure. No. 11
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FLUIDIZED-BED TECHNOLOGY
PAN COATING:
The pan coating process, widely used in
the pharmaceutical industry, is among the oldest
industrial procedures for forming small, coated
particles or tablets. The particles are tumbled in
a pan or other device while the coating material
is applied slowly. In pan coating, solid particles
are mixed with a dry coating material and the
temperature is raised so that the coating material
melts and encloses the core particles, and then
is solidified by cooling; or, the coating material
can be gradually applied to core particles
tumbling in a vessel rather than being wholly
mixed with the core particles from the start of
encapsulation.(Fig.No12)
Figure.No.12
Pan Coating
CENTRIFUGAL EXTRUSION:
Centrifugal extrusion processes generally
produce capsules of a larger size, from 250
microns up to a few millimeters in diameter. The
core and the shell materials, which should be
immiscible with one another, are pushed through
a spinning two-fluid nozzle. This movement
forms an unbroken rope which naturally splits
into round droplets directly after clearing the
nozzle. The continuous walls of these droplets
are solidified either by cooling or by a gelling
bath, depending on the composition and
properties of the coating material.(Fig.No.13)
Figure.No.13
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Centrifugal Extrusion
A dual fluid stream of liquid core and shell
materials is pumped through concentric
tubes and forms droplets under the influence
of vibration.
The shell is then hardened by chemical
cross
linkings,
cooling,
or
solvent
evaporation.
Different types of extrusion nozzles have
been developed in order to optimize the
process(25)
SPINNING DISK
Suspensions of core particles in liquid shell
material are poured into a rotating disc.(26)
Due to the spinning action of the disc, the
core particles become coated with the shell
material.
The coated particles are then cast from the
edge of the disc by centrifugal force.
After that the shell material is solidified by
external means (usually cooling).
This technology is rapid, cost-effective,
relatively simple and has high production
efficiencies.(Fig.No.14)
Figure.No.14
Spinning Disk
Due to the development and specialization of microencapsulation technologies and applications,
microencapsulation products differ in structure and terminology: (27) Table.No.2)
Table.No.2
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Terminology of microencapsulation products
Terminology
Description
Microcapsules
(narrow sense of
Meaning
Products of coating liquid
nuclei with solid walls.
Nanocapsules
Same structure as
microcapsules, but
smaller.
nm
Microspheres or
Microparticles
The cores and walls are
both solid. Often, there is
no
clear
distinction
between them: the thick
solid wall functions as a
porous matrix where
active substances are
embedded.
Same structure as
microspheres, but
smaller.
Lipid wall, often made of
Phospholipids and
cholesterol.
Subtypes: unilamellar
(one lipid layer) and
multilamellar (several
lipid layers).
Similar to Liposomes but
their membranes are
made of synthetic
amphiphylic molecules
(detergents).
µm
Nanospheres or
Nanoparticles
Liposomes
Niosomes
ENHANCING COATING FUNCTIONALITIES
WITH MICROCAPSULES
Microcapsules can be used in a wide variety of
applications [28, 29, 30], since the versatility of
microencapsulation technologies offers unlimited
combinations of core and shell materials for their
production. To date, few investigations have
been made into possible applications of
Size
range
µm
Schematic illustration
nm
µm
to
nm
microcapsules
in
functional
coating
developments. Microcapsules are applied onto
substrates in various ways. For example, they
may be sprayed over an existing coating layer,
perhaps to provide immediate release of
lubricants or perfumes. The most two common
process of applying microcapsules in coatings
are either to incorporate them into a coating
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formulation or by their electrolytic co-deposition
with metal ions (Fig. 15) 31, 32
Figure .No 15
Schematic diagram showing pathways for microcapsule incorporation into Coatings.
(a) Blending of microcapsules with binders;
(b) electrolytic co-deposition of Microcapsules with metallic ions
The mixing of microcapsules with coating
binders requires compatibility of the shell
material
with
the
binder.
Generally,
microcapsules are used in coatings for
controlled-release
applications,
but
microcapsules containing active ingredients such
as biocides can also be trapped inside a coating
matrix that will release the contents slowly over
time. Another interesting example is to use
microcapsules in the development of self-healing
coatings33. For this, microcapsules containing
monomer, cross linker or catalysts are
incorporated into a coating matrix such that,
when a coating ruptures, the microcapsules
along the rupture break open and release their
contents.
Subsequently,
the
monomer
polymerizes crosslink’s, and fills the damage,
thereby preventing further propagation. An
innovative
example
is
the
use
of
microencapsulated
phase-change
material
(PCM) particles in interior coatings for buildings
34,35
. During the day, as the temperature rises,
the core material melts and stores heat. During
the night, when the temperature falls, the heat
stored inside the capsules is released, thereby
reducing energy needs.
Commonly
used
coat
materials
in
microencapsulation:
At
Coating
Place,
coatings
are
customized to solve problems. Once desired
coat functions and coating material restrictions
have been established, a coating formulation can
be developed from a range of available coating
materials, modifiers, and solvents. The list of
coating materials shown below represents the
range of components that have been
successfully applied in coating formulations at
Coating Place. This list is not comprehensive;
there are many other materials that can be
applied. Coating materials may be applied
directly as a hot melt or via a solution,
suspension, dispersion, emulsion, colloid, or
latex. Solvent vehicles may be aqueous or
organic. (TABLE.NO.3)
Table.No.3
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commonly used coat materials in microencapsulation:
S.No
1
2
3
4
5
6
7
8
COMMONLY USED
COAT
Acacia
Acrylic polymers and copolymers
Ex: Polyacrylamide
Polymethyl methacrylate
Agar
Albumin
Alginates
Ex: sodium and calcium alginates
Aluminum monostearate
Carboxy vinyl polymer
MATERIALS
12-hydroxy stearyl alcohol
Polyamide
Ex: Nylon 6-10
Poly ( ε-caprolactone)
Poly dimethyl siloxane
Poly vinyl alcohol
Shellac
Stearic acid
Waxes
Ex: Bees wax
Carnauba wax
Spermaceti
Paraffin wax
Cellulose polymers
Ex: cellulose acetate
Cellulose acetate phthalate
Cellulose acetate butyrate
Ethyl cellulose
Hydroxy propyl cellulose
Hydroxy propyl methylcellulose
Methyl cellulose
Opadry® coating systems
Teflon® fluorocarbons
Surelease®
systems
fluoroplastics
Milk solids, Molasses , Nylon, Maltodextrins Shellac,
Stearines, Zein
APPLICATIONS OF
MICROENCAPSULATIONS:
In such industrial applications, the objective is
not to isolate the core completely but to control
the rate at which it leaves the microcapsule, as
in the controlled release of citric acid in the food
coating
Kynar®
Starches,
industry and chemical drugs in the pharma
industry and fertilizers in the agro industry.
Actually about any area in the industry could
beneficiate
from
microencapsulation
technologies. Microencapsulation can be found
in various fields (Fig No.16)
Figure.No.16.
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Applications Of Microencapsulation
Cell Immobilization:
In plant cell cultures microencapsulation, by
mimicking cell natural environment, improves
efficiency in production of different metabolites
used for medical, pharmacological and cosmetic
purposes. Human tissue are turned into bioartificial organs by encapsulation in natural
polymers and transplanted to control hormonedeficient diseases such as diabetes and severe
cases of hepatic failure. In continuous
fermentation processes immobilization is used to
increase cell density, productivity and to avoid
washout of the biological catalysts from the
reactor. This has already been applied in ethanol
and solvent production, sugar conversion or
wastewater treatment.
Beverage Production:
Today beer, wine, vinegar and other food
drinks production are using immobilization
technologies to boost yield, improve quality,
change aromas, etc...
Protection of Molecules from Other
Compounds:
Microencapsulation is often a necessity to
solve simple problem like the difficulty to
handle chemicals (detergents dangerous if
directly exposed to human skin) as well as
many other molecule inactive or incompatible
if mixed in any formulation. Moreover,
microencapsulation also allows preparing
many formulations with lower chemical loads
reducing significantly processes’ cost.
Drug Delivery:
After designing the right biodegradable
polymers, microencapsulation has permitted
controlled release delivery systems. These
revolutionary systems allow controlling the
rate, duration and distribution of the active
drug. With these systems, microparticles
sensitive to the biological environment are
designed to deliver an active drug in a sitespecific way (stomach, colon, specific
organs). One of the main advantages of such
systems is to protect sensitive drug from
drastic environment (pH,) and to reduce the
number of drug administrations for patient.
Quality and safety in food, agricultural &
environmental sectors:
Development of the “biosensors” has been
enhanced by encapsulated bio-systems used
to control environmental pollution, food cold
chain (abnormal temperature change).
Soil Inoculation:
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For example Rhizobium is a very interesting
bacterium which improves nitrate adsorption
and conversion. But inoculation is often
unsuccessful because cells are washed out
by rain. By cell encapsulation processes, it is
possible to maintain continuous inoculation
and higher cell concentration. This list is not
exhaustive, the nutraceuticals’ world could
be the last mentioned because of the growing
interest & increasing demand we have to face
in ingredients with health benefits which often
require improvement of their efficiency and
stability (e.g. probiotics, vitamins...) by
protecting and offering targeting release of the
active materials.
Applications of microcapsules in building
construction materials
An analysis of scientific articles and patents
shows numerous possibilities of adding
microencapsulated active ingredients into
construction materials, such as cement, lime,
concrete, mortar, artificial marble, sealants,
paints and other coatings, and functionalized
textiles. A summary of applications is presented
in (Fig.No.17)
Figure .No.17
Applications of microcapsules in building construction materials
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FUTURE PROSPECTS OF
MICROENCAPSULATION
o Microencapsulation, as its name suggests, is
the creation of a tiny capsule (or, in practice,
lots of tiny capsules), usually just microns in
diameter, containing a particular material. In
practice, microencapsulation entails placing a
spherical shell composed of a synthetic or
natural polymer completely around another
chemical. That shell delays or slows the
release of the core material. When the
polymer shell dissolves or is ruptured by
pressure, the material it encapsulates is
released.
o Microencapsulation is not new. It has been
around for decades in the form of spray
drying, spray chilling, freeze drying and
coacervation. But scientists believe that the
sector
has
innovated
rapidly.
The
microencapsulation sector is therefore fast
establishing itself at the cutting edge of food
and beverage flavor development. The use of
nanotechnology, which involves the study
and use of materials at sizes of millionths of a
millimeter, could increasingly be used in the
creation and development of flavors and
flavor systems in the future.
o Microencapsulated flavors are opening up
new food development possibilities never
before attempted “The Franken food that
o
o
o
o
improves you” in UK’s. Of these,
encapsulation technologies play a huge role
in their picture of the future of foods.
Microencapsulation of oil ingredients, like
omega-3, with sugar beet pectin could
provide an alternative to more traditional
encapsulating agents like milk proteins and
gum Arabic
Further research of microencapsulation, to
test
the
oxidative
stability
of
the
microcapsules over time as well as flavor
retention for aroma compounds.
Future prospects of microencapsulation of
islets of Langerhans used sodium alginate
and poly-l-lysine (PLL) to form the capsules
In addition to the familiar uses noted above,
microcapsules have found uses in the
pharmaceutical, agricultural, cosmetic, and
food industries and have been used to
encapsulate
oils,
aqueous
solutions,
alcohols, and various solids.
ACKNOWLEDGEMENTS
We acknowledged our management of Hindu
college of pharmacy and also very much thankful
to Professors A.SeethaDevi, K.Suria Prabha,
and P.MuthuPrasanna for giving constant
support.
REFERENCES
1.
2.
3.
Jackson L. S, Lee K, "Microencapsulation
and the food industry", Lebensmittel
Wissenschaft Technologie, Retrieved 199102-02.
Remuñán C, Alonso MJ,Microencapsulation
de
medicamento,
En.Vilá-Jato,
JL.Tecnología
Farmacéutica,Aspectos
fundamentales
de
los
systems
farmacéuticos
operaciones básicas,
Madrid: Ed. Síntesis, SA:577-609,(1997).
Boh.B,
Kornhauser,
A.Dasilva,Microencapsulation for pollution
4.
5.
6.
7.
prevention,
developing
support
for
introducing clean(er) pp: 205-222, (1996).
Boh, B., Sajovic, I., Voda, K.: Microcapsule
applications: patent and literature analysis
pp:85-156,(2003)
J.L. Luna-Xavier, E. Bourgeat-Lami, A.
Guyot, Colloid. Polym. Sci:279,947–958,
(2001)
W.F. Liu, Z.X. Guo, J. Yu, J. Appl. Polym.
Sci: 97(4), 1538–1544, (2005).
M. Okubo, H. Minami, Y. Jing, J. Appl
,Polym. Sci:89, 706–710, (2003).
This article can be downloaded from www.ijpbs.net
P - 530
ISSN 0975-6299
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Vol 3/Issue 1/Jan – Mar 2012
M.L.Soto-Portas,
J.F.
Argillier,
F.
Méchin,N. Zydowicz, Polym. Int: 52,522–
527, (2003).
B.Z. Putlitz, K. Land fester, H. Fischer, M.
Antonietti, Adv. Mater :13(7), 500–503,(
2001).
A.J.P. van Zyl, R.D. Sanderson, D. de WetRoos, B. Klumperman, Macromolecules:
36, 8621–8629,( 2003).
S. Benita, Microencapsulation:Methods and
Industrial applications, Marcel Dekker, Inc,
New York, (1996).
R.Arshady, Microspheres, Microcapsules
and Liposomes, Citrus Books, London,
United Kingdom, (1999).
M.W.Ranney,Microencapsulation
Technology,
Noyes
Development
Corporation, Park Ridge: 275(1969).
Stephen J. Dick, “The Biological Universe”:
pg.340(1999).
Leon Lachman, Herbert A. Lieberman,
Joseph L. Kanig,“The Theory and Practice
of Industrial Pharmacy”, 3rd edition, pp.420.
Mahmoud M. Ghorab a, Hossein Zia a,
Louis A. Luzzi a, Preparation of controlled
release anticancer agents I: 5-fluorouracilethyl cellulose microspheres, Journal of
Microencapsulation, 7(4), October: p 447 –
454(1990).
R. Ghaderi, A Supercritical Fluids
Extraction Process for the Production of
Drug Loaded Biodegradable Microparticles,
PhD
Thesis,
ACTA
Universitatis
Upasaliensis, Uppsala, (2000).
H. Liu, M.Z. Yates, Langmuir:18, 6066–
6070(2002).
P. Chambon, E. Cloutet, H. Cramail,
Macromolecules:37, 5856–5859(2004).
Sankar.C,Mishra.B,Development and in
vitro evaluations of gelatin A microspheres
of ketorolac tromethamine for intranasal
administration.Acta Pharm: 53(2): 101-10,
(2003).
Desai, K. G. H.1 Park, H. J.2, Preparation
of cross-linked chitosan microspheres by
spray drying: Effect of cross-linking agent
on the properties of spray dried
microspheres,
Journal
of
Microencapsulation: 22(4), June, p. 377395(19),( 2005).
22. Albertini B, Passerini N, Di Sabatino M,
Vitali B, Brigidi P, Rodriguez L, Polymerlipid based mucoadhesive microspheres
prepared by spray-congealing for the
vaginal delivery of econazole nitrate, Eur J
Pharm Sci, Dec 25,( 2008 ).
23. K. Lehmann, in: Microcapsules and
Nanoparticles in Medicine and Pharmacy
(Ed. M. Donbrow), CRC Press, Boca Raton
:pp. 73–97,( 1992).
24. D.E. Wurster, US Patent 2648609, and
September 8, through, Swapan Kumar
Ghosh,
Functional
coatings
and
Microencapsulation:
A
General
Perspective:P 22. (1953)
25. J.T.
Goodwin,
G.R.
Somerville,
Chemtech:623–626,( 1974).
26. R.E. Sparks, M. Norbert, US Patent
4675140, June 6, (1987).
27. Boh, B. Kornhauser, A., Dasilva, E
Microencapsulation
technology
applications: with special reference to
biotechnology: pp. 51-76,(1996).
28. R. Arshady, Microspheres, Microcapsules
and Liposomes, Citrus Books, London,
United Kingdom, (1999).
29. G.O. Fanger, Chemtech: 397–405,(1974).
30. H. Yoshizawa, KONA: 22, 23–31,(2004)
31. A. Dietz, M. Jobmann, G. Raf ler, Mat.wiss. u. Werkstofftech, 31, 612–615,(2000).
32. Z. Liqun, Z. Wei, L. Feng, J. Mater. Sci: 39,
495–499,( 2004).
33. E.N. Brown, S.R. White, N.R. Sottos,
J.Mater. Sci: 39, 1703–1710,( 2004).
34. J.F. Su, L.X. Wang, L. Ren, J. Appl.Polym.
Sci: 97(5), 1755–1762,( 2005).
35. M.N.A. Hawlader, M.S. Uddin, H.J. Zhu,Int.
J. Energy Re: 26, 159–171,(2002).
This article can be downloaded from www.ijpbs.net
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