Download M.Pharm. Dissertation protocol

IONOTROPIC GELATION TECHNIQUE:
AN APPROACH TO DESIGN AND
EVALUATE THE STAVUDINE GELLAN
GUM MICROBEADS
M.Pharm. Dissertation protocol
Submitted to the
Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.
By
Mahantesh .V. Kamalapur
Under the esteemed guidance of
Mr. J. S. Patil M.PHARM (PhD)
Asst. Professor
Department of Pharmaceutics
B.L.D.E.A’S COLLEGE OF PHARMACY, BIJAPUR
2010-2011
Rajiv Gandhi University of Health Sciences,
Bangalore Karnataka.
ANNEXURE II
PROFORMA FOR REGESTRATION OF SUBJECTS FOR DISSERTATION
1.
2.
Name of the Candidate and
Address
(In block letters)
Name of the Institution
Mr. MAHANTESH.V.KAMALAPUR
B.L.D.E.A’s COLLEGE OF PHARMACY,
BIJAPUR-586 103
3.
Course of study and subject
M.PHARM.--PHARMACEUTICS
4.
Date of admission to Course
23-05-2009
5.
Title of the Topic
IONOTROPIC GELATION TECHNIQUE:AN
APPROACH TO DESIGN AND EVALUATE
THE
STAVUDINE
GELLAN
GUM
MICROBEADS
6.
7.
Brief resume of the intended work :
6.1 Need for the study
Enclosure-I
6.2 Review of literature
Enclosure-II
6.3 Objectives of the study
Enclosure-III
Material and Methods :
7.1 Source of data
: Enclosure-IV
7.2 Method of collection of data (including sampling procedure, if any)
: Enclosure-IV
7.3 Does the study require any investigations or interventions to be conducted
on patients or other humans or animals? If so, please describe briefly.
: No
7.4
Has ethical clearance been obtained from your institution in case of 7.3
: No
8.
List of References (about 4-6)
9.
Signature of candidate
10.
Remarks of the guide
11.
Name & Designation of
(in block letters)
12.
: Enclosure-V
: Enclosure-VI
11.1
Guide
Shri. J.S. PATIL M.PHARM.(PhD)
Assistant Professor
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy,
BIJAPUR-586 103
11.2
Signature
11.3
Co-Guide (if any)
---
11.4
Signature
---
11.5
Head of Department
11.6
Signature
12.1
Remarks of the chairman & principal: This study can be carried out in our
laboratory
12.2
Signature
Enclosure-I
6. BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY
The main objective of any drug therapy is to achieve a desire
concentration of drug in blood or tissue, which is therapeutically effective and
non toxic for an extended period of time. This can be achieved by proper design
of sustained release dosage regime. Various approaches have been developed for
sustain release; microsbeads are the potential candidate for oral sustained release
of drug1.
Microspheres have been widely accepted as a means to achieve oral and
parentral controlled release drug delivery system. The ionotropic-gelation
technique, where, gelation was achieved with oppositely charged ions, acting as
a counter ion to form instantaneous beads thereby reduces the drug diffusion
during encapsulation process and improve the drug entrapment efficiency.2
Stavudine is the FDA-approved drug for clinical use for the treatment of
HIV infection, AIDS and AIDS-related conditions either alone or in
combination with other antiviral agents. Stavudine is typically administered
orally as a capsule and an oral solution. The virustatic drug has a very short halflife (1.30 h). The side effects of stavudine are dose-dependent and a reduction of
the total administered dose reduces the severity of the toxicity.
No work on stavudine microbeads has reported. And, hence, main aim
of the present study is to develop a sustained drug delivery system of Stavudine
using gellan gum and chitosan in order to increase its biological half life and to
determine the influence of formulation and preparation variables on
microparticles characteristics3.
Enclosure-ll
6.2 REVIEW OF LITERATURE
1) Chowdary et al., have developed microspheres of stavudine by water-inoil-in-oil (w/o/o) double emulsion solvent diffusion method using ethyl
cellulose and in combination with polyvinyl pyrrolidone. The prepared
microspheres were characterized by micrometric properties, drug
loading, Fourier transform infrared spectroscopy, X-ray powder
difractometry and scanning electron microscopy. The prepared
microspheres were white, free flowing and spherical in shape, stable in
nature, with 41-65% of drug entrapment efficiency4.
2) Chowdary et al., have developed A new emulsion gelation method to
prepare gel beads for a highly water-soluble drug metformin
hydrochloride using sodium alginate as the polymer. The gel beads
containing oil was prepared by gently mixing or homogenizing oil and
water phase containing sodium alginate which was then extruded into
calcium chloride solution to produce gel beads. The effects of factors
like type of oil and percentage of oil on the morphology and release
characteristics were investigated. The oil entrapped calcium alginate gel
beads
showed
good
sustained
release.
Scanning
electron
photomicrographs demonstrated minute oil globules on the beads and
also through the inner surface of the beads. The beads also showed
floating behavior depending on the type of the oil that have been used for
the preparation5.
3) Silva
et
al.,
have
developed
Alginate
microspheres
by the
emulsification/internal gelation technique with the objective of
preserving protein stability during encapsulation procedure. The
influence of process and formulation parameters was evaluated on the
morphology and encapsulation efficiency of insulin. The in-vitro release
of
insulin
from
microspheres
was
studied
under
simulated
gastrointestinal conditions. Insulin encapsulation efficiency, near 75%,
was not affected by emulsifier concentration, mixer rotational speed and
zinc/insulin hexamer molar ratio but decreased either by increasing
internal phase ratio and calcium/alginate mass ratio or by decreasing
acid/calcium molar ratio and alginate concentration. A high insulin
release, above 75%, was obtained at pH 1.2 and under simulated
intestinal pH a complete dissolution of microspheres occurred6.
4)
Enas et al., have developed Floating famotidine loaded mineral oilentrapped emulsion gel (MOEG) beads by the emulsion–gelation method
and parameters such as drug uniformity, drug entrapment efficiency
(DEE) and in-vitro drug release were studied. The results clearly
indicated that retardation of drug release for 4 h was achieved by the oil
hydrophobic diffusional barrier, especially in the presence of the
compact network of alginate beads. Calcium alginate beads containing
20% oil and 2:1 drug: polymer ratio, showed an optimum DEE of
88.32%. When evaluated in-vivo, this formula displayed superior
antiulcer activity (>2) over drug suspension or marketed conventional
tablets7.
5) Khazaeli et al.,have developed Formulation of ibuprofen beads to reduce
its gastric ulcerogenicity. Hence, Ca-alginate ibuprofen beads, through
ionotropic gelation have been investigated. For this purpose, different
cross- linking agents including: Ca2+, Ba2+, Mn2+, Co2+, Sn2+ and
Pb2+, were used for bead preparation. Next, characterization of the
beads, size distribution, and encapsulation efficiency within the beads,
the bead swelling and the drug release kinetic were investigated. Results
showed that only Calcium ion is suitable for the formation of ibuprofen
beads. A good swelling profile for beads in phosphate buffer (pH=7.4)
and the lack of swelling in hydrochloric acid (pH= 1.2),was seen. The
drug release studies showed a rapid and complete ibuprofen release from
the beads, especially those prepared from Na-alginate (2%) and Cachloride (2%), in phosphate buffer medium8.
Enclosure- IIl
6.3 OBJECTIVES OF THE STUDY
The main objective of study is to design and evaluate the Stavudine
microsbeads for its improved biological half-life and release of drug over
extended period of time form the formulation.
1. To prepare microbeads of Stavudine by using ionotropic-gelation
method using gellan gum and chitosan as the rate controlling matrix
materials, and hydroxypropylmethylcellulose phthalate as a coating
material.
2. To perform the percentage encapsulation efficiency of the
microbeads with suitable methods.
3. To perform in-vitro drug release study using USP XXIII model
(ElectroLab, TDT 06P) of different formulations and analyzed them
for drug release using UV-Visible spectroscopy at 266 nm
(Pharmaspec 1700, Shimadzu, Japan).
4. To evaluate the microsbeads for particle size, micromeretic profiles.
5. To detect the drug-polymer compatibility by performing Fourier
Transform Infrared Spectroscopy(FTIR).
6. To characterize the formulation for thermal behavior(DSC), and
surface morphology(SEM).
7. To perform the study of swelling index of the prepared beads.
8. To conduct the stability study of the prepared beads as per ICH
guidelines.
Enclosure IV
7. MATERIALS AND METHODS
7.1 SOURCE OF DATA
Studies on design of Stavudine microbeads are laboratory based. Data
will be generated by performing lab experiments and by referring various
journals, abstracts and textbooks etc.
7.2
METHOD OF COLLECTION OF DATA
The data is planned to collect from the laboratory experiments which
includes.
1. The microbeads will be prepared using ionotropic-gelation technique.
2. Microbeads will be characterized by SEM, FTIR study using Fourier
Transform Infrared Spectrophotometer (FTIR-8400 S Shimadzu, Japan),
and DSC and data will be collected.
3. The particle size, drug entrapment efficiency will be carried out and data
will be collected.
4. Microbeads will be subjected to in-vitro drug release study using
dissolution apparatus and data will be collected.
7.3 Dose the study requires any investigation or intervention to be conducted
on patient or other humans or animal? If so please describe briefly.
---- Not under the plan of work---7.3 Has ethical clearance been obtained from your institution in case of 7.3?
------- Not applicable-------
Enclosure V
8. LIST OF REFERENCE
1. Shabaraya AR, Narayanacharyulu R. Design and Evaluation of Chitosan
Microsphere of Metoprolol Tartarate for Sustained release. Indian J.
Pharm. Sci. 2003; 65(3):250-252.
2. Das KD, Maurya DP. Microencapsulation of Water-Soluble Drug by
Emulsification-Internal Gelation Technique. Indian J. Pharm. Res. 2009
Jan; 43(1):28-38.
3. Sahoo SK, Mallick AA, Barik BB, Senapati PC. Formulation and invitro Evaluation of Eudragit® Microspheres of Stavudine. Tropical J. of
Pharm. Res. 2005 June; 4(1): 369-375.
4. Chowdary KPR, Koteshwara RN, and Malathi K. Ethyl cellulose
microspheres of gliplizide: characterization, in-vitro and in-vivo
evaluation. Indian J. Pharm Sci. 2004; 66: 412- 416.
5. .Choudhury PK, Kar M. Preparation of Alginate Gel Beads Containing
Metformin Hydrochloride Using Emulsion-Gelation Method. Tropical J.
of Pharm. Res. 2005; 4(2):489-493.
6. Silva CM, Ribeiro A, Figueiredo IV, Goncalves AR, Veiga F. Alginate
Microspheres Prepared by Internal Gelation: Development and Effect on
Insulin Stability. Int. J. of Pharm. 2006; 311:1-10.
7. Enas ME, Awad AS, Mansour S. Ionotropicically emulsion gelled
polysaccharide beads: prepration, in-vitro and in-vivo evaluation.
Carbohydrate polymers. 2008; 75:135-142.
8. Khazaeli P, Pardakhty A, Hassanzadeh F. Formulation of Ibuprofen
Beads by Ionotropic Gelation. Iranian J. of Pharm. Res. 2008; 7(3):163170.
ENCLOSURE-VI
10) Remarks of the Guide
The present work is aimed to design and evaluate the stavudine gellan
gum microbeads by ionotropic gelation technique as a sustained release
system. It is widely used as a antiviral agent. The drug is practically
soluble in water. Hence, the main aim of the present study is to develop
a sustained drug delivery system of stavudine using gellan gum and
chitosan in order to increase its biological half life and to determine the
influence of formulation and preparation variables on microparticals
characteristics.
The proposed study can be carried out in the laboratory.
J.S.PATIL., M.PHARM(PhD)
Asst. Professor
Research Guide
.