FORMULATION AND EVALUATION OF FLOATING
MATRIX TABLET OF ESOMEPRAZOLE
M.PHARM DISSERTATION PROTOCOL
Submitted to
Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka
By
PATEL ISHVAR C.
(M.PHARM)
Under the Guidance of
MR. HARIPRASANNA R.C.
M.PHARM (PH.D)
DEPARTMENT OF PHARMACEUTICS
R.M.E.S’s COLLEGE OF PHARMACY,
GULBARGA-585102
2009-2010
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,
KARNATAKA.
CURRICULUM DEVELOPMENT CELL
CONFORMATION FOR REGISTRATION OF SUBJECT FOR DISSERTATION
Registration No.
:
Name of the Candidate
:
Patel Ishvar Chotubhai
Address
:
R.M.E.S’s College of Pharmacy
Gulbarga, Karnataka.
Name of the Institution
:
R.M.E.S’s College of Pharmacy
Gulbarga, Karnataka.
Course of Study and Subject
:
M.Pharma in Pharmaceutics
Date of Admission to the Course
:
12th Oct. 2009
Title of the Topic
:
Formulation and Evaluation of Floating Matrix
Tablet of Esomeprazole.
Brief resume of the intended work
:
Enclosed
Signature of the student
:
Guide Name
:
Prof. Hariprasanna R. C. M.Pharm (Ph.D)
Remarks of the Guide
:
Recommended for approval
Signature of the Guide
:
Co-Guide Name
:
Signature of the Co-Guide
:
HOD Name
:
Signature of the HOD
:
Director/Principal Name
:
Prof. Kishoresingh K.Chatrapathi M.Pharm Ph.D
Mobile No
:
+919880200905
Director/Principal E-mail ID
:
[email protected]
Remarks of Director/ principal
:
Recommended for approval
Director/Principal Signature
:
Mr. Mohan V. Kodli M.Pharm
Prof. Hariprasanna R.C. M.Pharm(Ph.D)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE, KARNATAKA
BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
Name of Candidate and address (In
block letters)
2.
Name of Institution
3.
Course of Study and Subject
4.
Date of Admission to Course
5.
Title of the Topic
PATEL ISHVAR CHOTUBHAI
C/O RMES’s COLLEGE OF
PHARMACY BALAJI NAGAR, OLD
JEWARGI ROAD, GULBARGA-02
RMES’s COLLEGE OF PHARMACY
M.PHARMA (PHARMACEUTICS)
12TH OCT 2009
FORMULATION AND EVALUATION
OF FLOATING MATRIX TABLET
OF ESOMEPRAZOLE
6.
BRIEF RESUME OF THE INTENDED WORK
6.1
Need for the study:
The development of oral sustained and controlled release formulation offer benefits like
controlled administration of therapeutic dose at the delivery rate, constant blood levels of the drug,
reduction of side effects, minimization of dosing frequency and enhancement of patient
compliance.1
Gastro retentive system can remain in the gastric region for several hours and hence
significantly prolong gastric residence time of drug. Prolong gastric retention improves
bioavailability, reduce drug wastage, and improves solubility of drug that are less soluble in a high
pH environment. It has application also for local drug delivery to the stomach and proximal small
intestine. Gastro retention helps to provide possibilities and substantial benefits for patients2,
appealing for those diseases, the symptoms of which recur mainly at night time or early morning,
such as gastritis, higher healing rates of erosive esophagitis, healing gastric /duodenal ulcer inhibit
H.pylori, zolling-ellison and syndrome in GERD.3
Esomeprazole 6-methoxy-2-[(4-methoxy-3, 5-dimethyl pyridine-2-yl) methylsulfinyl]-1Hbenzimidazole, is an important anti-ulcer, antihistamine and enzyme inhibitor also with proton
pump inhibitor properties whose mechanism of action is to suppress the gastric acid secretion by
specific inhibition of the H+/K+ - ATPase in the gastric parietal cell. By acting specifically on the
proton pump, esomeprazole block the final step in acid production, thus reducing gastric acidity. It
is used in the treatment of acid-reflux disorder (GERD) and peptic ulcer disease. Esomeprazole
drug plasma half-life 1-1.5 hours with 90% of absorption4. Floating matrix tablet provides
increased gastric residence and thereby a longer period of residence of the drug delivery system in
the gastrointestinal tract.5 The drug must be administered 20-40mg once day for 4-8 weeks in case
of GERD and Erosive gastritis.6
The aim of this work is to design floating drug delivery system with gas generating agents
and hydrophilic agents like HPMC and Esomeprazole as model drug.
{
6.2
Review of Literature:
Literature survey was carried out on the proposed research work by referring various
Scientific Research Journals, Helinet facilities and science direct.
1. Arora Shweta et. al., Floating drug delivery system- A Review to develop an efficient
floating drug delivery (FDDS) was to compile the recent literature with special focus on
the principle mechanism of floatation to achieve gastric retention.2
2. Singh Brahma N. et. al., Floating drug delivery system; an approach to oral controlled
drug delivery via gastric retention have been made for rate- controlled drug delivery by
overcoming physiological properties, such as gastric residence times (GRT) and
unpredictable gastric emptying time (GET).7
3. Xiao Qiang Xu et. al., floating matrix dosage form for phenoporlamine HCL based on gas
forming agent; In this work the in-vitro an in-vivo evaluation of formulation was done.
Formulation showed increased bioavailability with good floating properties.8
4. Sunthongjeen Srisagul et. al., design and evaluation of floating multi-layer tablets based
on gas formation were developed. In this work gas generating agent (sodium bicarbonate),
protective layer (HPMC) and acrylic polymers (eudragit RL 30 D, NE 30 D) were used.
Formulation showed good floating properties and sustained drug release was achieved.9
5. Baumgartner Sasa et. al., Optimization of floating matrix tablets and evaluation of their
gastric residence time. In this work tablet containing hydroxyl propyl methyl cellulose
(HPMC), drug and different additives were compressed, and incorporation of gas
generating agent together with microcrystalline cellulose. Formulated tablet didn’t adhere
tablet to the stomach mucus and that the mean gastric residence time was prolonged.10
6. Streuble A. et. al., Floating matrix tablets based on low density foam powder; effects of
formulation and processing parameters on drug release. In this work different types of
matrix polymers were studied; hydroxypropyl methylcellulose, polycrylates, sodium
alginate, corn starch, carrageenan, guar gum and gum Arabic. Formulation of floating
behaviour of low density drug delivery showed accurate control of the drug release
patterns.11
7. Talwar Naresh et. al., Orally administered controlled drug delivery system providing
temporal and spatial control. In this work various gas generating component, a swelling
agent, viscolyzing agent, and optionally a gel forms polymer were used, causing the tablet
or capsule to be retained in the stomach or upper part of the small intestine (spatial
control).5
8. Jaimini M. et. al., Formulation and Evaluation of Famotidine floating tablets was
reported. Different grades of Methocel K100 and Methocel K15M were used for gel
forming properties, sodium bicarbonate was incorporated as gas generating agent. The
drug release from the tablet was sufficiently sustained and non-Fickian transport of drug
from tablets was confirmed.12
6.3
Objectives of the study:
1. Development of the floating tablet of esomeprazole using gas generating agent like
sodium bicarbonate, citric acid, tartaric acid and hydroxypropyl methylcellulose(HPMC)
is hydrophilic polymers.
2. Esomeprazole floating tablet is prepared by using direct compression method and wet
granulation method.
3. Evaluation of prepared floating tablet such as floating time, drug content, drug polymer
interaction and in-vitro evaluation study.
4. Provides increased gastric residence time and thereby a longer period of drug delivery
system in GI tract.
5. Delivers the drug at controlled rate such that the drug is delivered over period of time.
6. It not only reduces the frequency of dosing but may also reduce the severity and
frequency of side effects.
7.
MATERIALS AND MTHODS:
7.1
Materials
Drugs: Esomeprazole
Swelling agent: Cross-linked polyvinyl pyrrolidone or cross-linked sodium carboxy
methyl cellulose.
Gas generating component: calcium carbonate and carbonates sodium bicarbonates or
sodium hydrogen carbonate or potassium hydrogen carbonate.
Other polymers: Hydroxypropyl methylcellulose, carbopol, Eudragit NE, Chitosan
Other excipients: Lactose, mannitol, dextrose, sorbitol and water soluble diluents such
as starch, microcrystalline, powered cellulose or lubricants such as talc, citric acid,
tartaric acid or ascorbic acid, magnesium state.
Equipments:
UV/Visible spectrophotometer 1700
Digital cover head stirrer electronic balance
Thermostatic Hot plate with magnetic stirrer
Electrolab dissolution apparatus
Punching machine.
Screw gauge, etc.
7.2
Method:
Preparation of Esomeprazole floating matrix tablet5:
The floating matrix tablet of the Esomeprazole will be prepared using above listed
materials by direct compression and wet granulation.
Pre compression parameters:
 Angle of repose
 Bulk density
 Top density
Post compression parameters:
 Weight variation
 Hardness
 Friability
 Drug content estimation
 In-vitro drug release
 Drug-polymer interaction
 Floating lag time
The in vitro buoyancy was determined by floating lag time, per the method described
by Rosa et al the tablets were placed in 100ml beaker containing 0.1N HCl. The time
required for the tablet to rise to the surface and float was determined as floating lag
time.13
7.3
Dose the study require any investigation or intervention to be conducted on patient
or other humans or animals? If so, please describe briefly.
-- Not under the plan of the work—
7.4
Has ethical clearance be obtained from your institution in case of 7.3
-- Not Applicable—
8. LIST OF REFERENCES.
1. Chien YW. Controlled and Modulated Release Drug Delivery System in Swarbrik J,
Boylan JC (Eds.). Encyclopaedia of Pharmaceutical Technology, Marcel Dekker, New
York, 1990: 281-313.
2. Arora Shweta, Ali Javed, Ahuja Alka, Khar Roop K. and Baboota Sanjula. Floating
Drug Delivery System: A review. AAPS PharmSciTech. 2005; 06(03): E372-E390.
3. Tripathi K D. Essential of Medical Pharmacy. 2003; (5):593.
4. http://www.drugbank.com/esomeprazole
5. Talwar Naresh, Sen Himardi,Staniforth John N. Orally Administered controlled drug
delivery system providing temporal and spatial control. 1998.
6. Advance Drug Review, July 2008: Issue IX; 161.
7. Singh Brahma N, Kim Kwon H. Floating drug delivery systems: an approach to oral
controlled drug delivery via gastric retention. Journal of Controlled release. 2000;
63:235-259.
8. Xiao Qiang Xu, Minije Sun, Feng Zhi, Yiqiao Hu. Floating matrix dosage form for
phenoporlamine HCL based on gas forming agent: In vitro and in vivo evaluation in
healthy volunteers. Int J Pharm. 2006; 310:139-145.
9. Sunthongjeen Srisagul, Sriamornsak Pornsak, Puttipipatkhachorn Satit. Design and
evaluation of floating multi-layer tablets based on gas formation. Eur. J Pharm and
Biopharm 2008; 69:255-263.
10. Baumgartner Sasa, Kristl Julijana, Vrecer Franc, Vodopivec Polona, Zorko Bojan.
Optimization of floating matrix tablets and evaluation of their gastric residence time.
Int J Pharm. 2000; 195:125-135.
11. Streuble A, Siepmann J, Bodmeier R. Floating matrix tablets based on low density
foam powder; effects of formulation and processing parameters on drug release. Euro.
J Pharm Sci. 2003; 18:37-45.
12. Jaimini M, Rana A.C, Tanwar Y.S. Formulation and Evaluation of Famotidine floating
tablets. Current Drug delivery, 2007; 4:51-55.
13. Dave BS, Amin AF, Patel MM. Gastro retentive Drug delivery system of Ranitidine
hydrochloride: Formulation and in vitro evaluation. AAPS PharmSciTech. 2004; 5(2):
article 34.
9
Signature of candidate.
[PATEL ISHVAR CHOTUBHAI]
10
Remarks of the Guide
11
Name & Designation of
(in block letters)
11.1 Guide
MR. HARIPRASANNA R. C.
M.PHARM (PH.D)
PROFESSOR AND HEAD OF
DEPT. OF PHARMACEUTICS,
RMES’S COLLEGE OF PHARMACY,
OLD JEWARGI ROAD,
GULBARGA-585102.
11.2 Signature
11.3 Co-Guide
MR. MOHAN V. KODLI
M.PHARM.
LECTURER,
DEPT. OF PHARMACEUTICS,
RMES’S COLLEGE OF PHARMACY,
OLD JEWARGI ROAD,
GULBARGA-585102.
11.4 Signature
12
12.1 Remarks of the Chairman and
Principal
12.2 Signature
PROF. KISHORESINGH K. CHATRAPATHI
DIRECTOR/PRINCIPAL
RMES’S COLLEGE OF PHARMACY, GULBARGA