PREPARATION AND EVALUATION OF VALSARTAN LOADED MICROSPHERES FOR SITE SPECIFIC DRUG DELIVERY
M. Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore.
By
Murali.Y.D
B. Pharm
UNDER THE GUIDANCE OF
M.A.SALEEM
Asst Professor
PG Dept. of Pharmaceutics
DEPARTMENT OF PHARMACEUTICS
LUQMAN COLLEGE OF PHARMACY, GULBARGA
2010-11
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate & Address(In block letters) / murali.y.d
S/O DAYANANDA AT POST: YALANADU
HULIYAR (H). TQ: CHIKKANAYAKANAHALLI
DIST: TUMAKUR -57221
2. / Name of the Institution / LUQMAN COLLEGE OF PHARMACY
P&T Colony, Old Jewargi Road,
GULBARGA-585 102. KARNATAKA STATE
3. / Course of Study and Subject / M.PHARM. (PHARMACEUTICS)
4. / Date of Admission to Course / 06th June 2010
5. / Title of the Topic / “PREPARATION AND EVALUATION OF VALSARTAN LOADED MICROSPHERES FOR SITE SPECIFIC DRUG DELIVERY”
6.
/ Brief Resume of the Intended Work6.1 / Need for the study:
Controlled drug delivery system (technology) represents one of the frontier areas of science which involves multidisciplinary scientific approach, contributing to human health care. These delivery systems offer numerous advantages compared with conventional dosages forms, which include improved efficacy, reduce toxicity and improved patient compliance and convenience. Microspheres have gained in popularity as oral drug delivery system because of more uniform distribution of drug in the gastrointestinal tract, more uniform drug absorption, reduced local irritation and elimination of unwanted intestinal polymeric material1.Using innovative microencapsulation technologies and varying the co-polymer ratio, molecular weight of the polymer etc. microspheres can be developed into an optimal drug delivery system which can provide desired release profile. Microspheres based system may increase the life span of active constituents and control the release of bioactive agents2. Microspheres are characteristically free following powders ideally having a particle size less than 200µm. Polymeric microspheres have attracted considerable attention as drug carriers for controlled release system. Particulate carriers are ideal in providing a constant therapeutic and non toxic level of drug. Various protein, polysaccharide and other polymeric materials have been investigated as drug carriers and many techniques have been pointed out to synthesis nanoparticles, micro particles and beads3. Use of natural polymer in the preparation of microspheres has gained the interest in the last two decades. Most commonly used natural biodegradable polymers are chitosan, carragenan, gelatin, collagen etc. which finds a wide array of pharmaceutical applications due to its low production cost, biodegradability, and non toxic nature4.
Valsartan is a specific angiotensin II antagonist is used alone or with other antihypertensive agent to treat hypertension, to reduce cardiovascular motility in the patients with left ventricular dysfunction following myocardial infraction and in the management of heart failure. The terminal elimination half life is about 5-9 hours. The oral dose is from 40-160mg in divided doses, commercially available as 40mg, 80mg and 160mg tablet5,6. Valsartan is poorly water soluble drug belongs to BCS-II category and particularly absorbed from alkaline pH. In the present study an attempt will be made to prepare and evaluate valsartan loaded microspheres as site specific drug delivery system in the effective management of hypertension.
6.2 / Review of Literature:
Extensive literature survey was carried out on the proposed research work by referring various scientific journals, internet and helinet facilities.
Ø Ragavendra NGR et al1., reported uniform distribution and absorption of drug and elimination of unwanted intestinal retention of polymeric material, when compared to non disintegrating single unit dosage form.
Ø Shina VR et al2., studied innovative microencapsulation technologies by varying the copolymer ratio, molecular weight of the polymer etc, and concluded that microspheres can be developed into an optimal drug delivery system which will provided the desired release profile.
Ø Pandey R et al7., prepared the microspheres using natural polymers and discussed about the capability of natural polymers providing a sustained release and therapeutic benefit for maintaining standing drug level in plasma.
Ø Saravanan M et al8., formulated and evaluated diclofenac sodium gelatin magnetic microspheres for intra-arterial administration and concluded that the release of drug can be enhanced from the gelatin microspheres.
Ø Zindal SK et al9., studied hydroxy propyl methyl cellulose acetate succinate as enteric polymer in the preparation of insulin microspheres.
Ø Rameshbabu V et al10., prepared sodium alginate-methycellulose blend microspheres by water in oil emulsion method for controlled release of nifedipine and prepared microspheres were characterized by differential scanning calorimetry and scanning electron microscopy.
Ø Chang Y et al.,11 prepared gelatin microsphere encapsulated with non peptide ginsenoside and indicated that intramuscular injection of gelatin microsphere successfully stimulate the growth of new microvessels or increase in myocardial collateral blood flow and preserve the infracted LV function and enhance myocardial perfusion.
6.3 / Objectives of the Study:
The preparation of valsartan loaded microspheres is planned with following objectives.
Ø To optimize the ratio of core to coat polymer using natural and enteric coated polymer.
Ø To prepare the microspheres by emulsification-ionotropic gelation / complex co-acervation.
Ø To study the polymer interaction by IR and the surface morphology will be studied by SEM.
Ø To evaluate the microspheres for micromeretic properties and flow properties.
Ø Drug entrapment efficiency, water uptake and invitro drug release.
Ø To study the effect of different ratios of core to coat polymer and method of preparation on particle size, drug loading efficacy and invitro release.
Ø To perform stability studies as per ICH guidelines.
7. / 7.1 / Materials And Methods
Materials
Drugs: Valsartan
Polymer: Natural origin like Chitosan/Gelatin/Albumin/gums.
Enteric coat polymer CAP(cellulose acetate phthalate), hydroxy propyl methyl cellulose acetate succinate.
Additives: Trypolyposphate/Genipine/Salt of mono or divalent cations.
All other chemicals will be use of analytical grade.
Apparatus:
Ø UV/Visible spectrophotometer 1700 (Shimadzu)
Ø Electronic balance sheet (Shimadzu corporation BL-220H)
Ø Single pan electronic balance Dhona 200D
Ø Electro lab dissolution apparatus(USP XXIII)
Ø Digital Over head stirrer
Ø Ultra Sonicator (Flexit)
7.2 / Methods:
Ø UV spectrophotometric estimation of valsartan.
Ø The valsartan loaded microspheres will be prepared by emulsification-ionotropic gelation/complex co-acervation.
Ø The valsartan loaded microspheres will be characterized by IR and SEM.
Ø Microspheres will be evaluated for flow properties (angle of repose, hausner ratio) micromeritic properties(particle size, size distribution), drug loading efficacy, water uptake, and in-vitro drug release study(by using dissolution apparatus)
7.3 / Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so please describe briefly.
------Not under the plan of the work ------
7.4 / Has ethical clearance been obtained from your institution in case of 7.3
------Not applicable------
8. / List of References
1. Raghavendra NGR, Kulkarni U, Deshmukh A, Suresh DK. “Preparation and Characterization of Ionotropic Cross-Linked Chitosan Microparticles for controlled release of Aceclofenac’’. Int. J Pharm Sci Drug Res.2010;2(2):107-111.
2. Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumria R, Bansal K, Dhawan S. “Chitosan microspheres as a potential carrier for drugs’’. Int. J Pharm.2006; 274:1-33.
3. Bulgarelli E, Forni F, Bernabei MT. “Effect of matrix composition and process conditions on casein-gelatin bead floating properties’’. Int. J Pharm.2008;198:157-165.
4. Dhawan S, Singla AK, and Sinha VR. “Evaluation of Mucoadhesive properties of Chitosan Microspheres prepared by Different methods’’. APPS PharmSciTech. 2004;5(4):1-7.
5. Sweetman SC. The editor Martindale: The complete drug reference 35th edn, London: Pharmaceutical press 2007;1277.
6. http://www.drugbank.ca/drugs/DB00177.
7. Pandey R, Khuller GK. “Chemotherapeutic potential of alginate-chitosan microspheres as anti-tubercular drug carriers’’. J Antimicrobial Chemo.2004;53:635-640.
8. Saravanan M, Anbu J, Maharajan G, Pillai KS. “Targeted delivery of diclofenac sodium via gelatin magnetic microspheres formulated for intra-arterial administration’’. J Drug Target. 2008; 16(5):366-378.
9. Jindal SK, Singh M, Goswami M. “Formulation and evaluation of insulin enteric microspheres for oral drug delivery’’. Acta Pharmaceutica Sciencia.2009;51:121-127.
10. Ramesh VB, Sairam M, Kallappa M, Hosamani, Aminabhavi TM. “Preparation of sodium alginate-methylcellulose blend microspheres for controlled release of nifedinpine’’. Carbohydrate polymers.2007;69:241-250.
11. Yang H et al., “Gelatin microspheres encapsulated with nonpeptide angiogenic agent, ginsenoside Rg1, for intramyocardial injection in a rat model with infracted myocardium’’. J Cont. Rel.2007;120:27-34.
9. / Signature of Student / Murali.Y.D
10. / Remarks of the Guide / The proposed work is a Novel drug delivery system for site specific delivery of Valsartan. Hence, recommended for registration.
11. / Name & Designation of (in block letters)
11.1 / Guide / M.A.SALEEM M. Pharm
ASST. PROFESSOR
PG. DEPT. OF PHARMACEUTICS,
LUQMAN college of pharmacy,
P&T Colony, Jewargi Road,
gulbarga.
11.2 / Signature
11.3 / Co-guide
11.4 / Signature
12. / 12.1 / Remarks of the Chairman & Principal / We will provide all the necessary facilities required for the proposed research work. So, recommended for registration
12.2 / Signature