EVALUATION AND FORMULATION OF BUCCAL PATCHES FOR METFORMIN A SYNOPSIS

SUBMITTED TO

UTTARAKHAND TECHNICAL UNIVERSITY In Partial Fulfillment Of Degree Of BACHELOR DEGREE OF PHARMACY BY MONALISHA BANERJEE

SUPERVISOR. DR. (PROF)VINEY CHAWLA G.I.S.I.P.S .DEHRADUN

CO-SUPERVISOR. ASST.PROFESSOR Miss.STUTIE PATHAK ANAND

GYANI INDER SINGH INSTITUTE OF PROFESSIONAL STUDIES DEHRADUN ,UTTARAKHAND

Content
Introduction Literature Survey Drug Profile Polymer Profile Aim and Objective Method Evaluation References

Introduction
Buccal delivery of drug provides an attractive alternative to the oral route of drug administration. Buccal drug delivery offers a safer method of drug delivery, since drug action can be promptly terminated in case of toxicity by removing the dosage from the buccal cavity. It is also possible to administer drugs to patients who cannot be given drugs orally for one reason or other. Well defined bioadhesion is the ability of a material (synthetic or biological) to adhere to a biological tissue for an extended period of time.

Advantage of Buccal Patche: 1)Patient can control the period of administration or terminate delivery in case of emergencies. 2)Drug bypaas first pass metabolism so increase bioavailability. 3)The buccal drug delivery

systems easily administered into the buccal cavity.Rapid onset of action. 4) Drug release from prolong period of time. 5) Oral mucosa has rich blood supply.

 Oral mucosal sites: 1) Sublingual delivery: is the administration of the drug via the sublingual mucosa (the membrane of the ventral surface of the tongue and the floor of the mouth) to the systemic circulation. 2) Buccal delivery: is the administration of drug via the buccal mucosa(the lining of the cheek)to the systemic circulation. 3) Local delivery: for the treatment of conditions of the oral cavity, principally ulcers, fungal conditions and periodontal disease.

Limitation of Buccal Patches:

1) The area of absorptive membrane is relatively smaller. If the effective area for absorption is dictated by the dimensions of a delivery system, this area then becomes even smaller. 2) The area of absorptive membrane is relatively smaller. If the effective area for absorption is dictated by the dimensions of a delivery system, this area then becomes even smaller. 3) Drug characteristics may limit the use of the oral cavity as a site for drug delivery.

Literature Survey
Patel et al (2009) By using PVA (10% w/v), chitosan (1% w/v) and PVP (5% w/v) solution in water which were mixed together in a determined ratio and stirred continuously until a clear solution was obtained. Then polyethylene glycol 400 (PEG-400) (2% w/w) was mixed uniformly to obtained a clear viscous liquid. This solution was taken in a petridish and dried in an oven maintained at 40C till a flexible patch was formed

Chaudhary et al.(2010) Drug was loaded after dispersion in 5ml phosphate buffer. Drug was added in polymeric dispersion of buccal patch formulation with continuous stirring. When drug was homogenously dispersed or dissolved solution was poured

in petridish. The backing membrane was prepared by dissolving ethyl cellulose (5%) in mixture of acetone and isopropyl alcohol (60:40). Glycerol (5%) was added as plasticizer. The patches were evaluated for weight uniformity, thickness, swelling index, surface pH, mucoadhesive strength and mucoadhesive time and folding endurance. Use of sodium alginate with carbopol-934 in presence of glycerol (plasticizer) showed promising results. In vitro drug release was found to be 82% through cellophane membrane and 70.78 % through buccal mucosa with suitable mucoadhesive strength and mucoadhesive time.

Dharani et al. (2010) using hydroxy propyl methyl cellulose E15 (HPMC E15) and 20 ml of (1:1) solvent mixture of dichloromethane and methanol was added. Propylene glycol was added to this mixture. Ondansetron hydrochloride was dissolved in 5 ml of solvent mixture, added to the polymer solution and mixed well. Patches were carried out in oven placed for drying in 8 hrs.

Drug Profile
Metformin is the only antidiabetic drug that has been conclusively shown to prevent the cardiovascular complications of diabetes. It helps reduce LDL cholesteroland triglyceride levels, and is not associated with weight gain. As , metformin is one of only two oral antidiabetics in the World Health Organization Model List of Essential Medicines (the other being glibenclamide) Clinical data Trade names Glucophage, Etform FDA Professional Drug AHFS/Drugs.com Information Medline Plus a696005 Licence data US FDA link Pregnancy cat C (AU) B (US) Formula C4H11N5 Mol. mass 129.16364 Routes oral

Systematic (IUPAC) name

N,NDimethylimidodicarbonimidi diamide

Pharmacokinetic data Bioavailability Protein binding Metabolism Half-life Excretion

5060% Minimal Not by liver 4-8.7 hours Urine (90%)

Combinations with other drug: When used for type 2 diabetes, metformin is often prescribed in combination with other drugs. Several are available as fixed dose combinations, also with the purpose of reducing pill burden and making

administration simpler and convenient. Pharmacokinetics: Metformin has an oral bioavailability of 5060% under fasting conditions, and is absorbed slowly.Peak plasma concentrations (Cmax) are reached within one to three hours of taking immediate-release metformin and four to eight hours with extended-release formulations.

Polymer Profile
Active ingredient. B. Polymers (adhesive layer):- Hydroxy ethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, carbopol and other mucoadhesive polymers. C. Diluents:- Lactose DC is selected as diluent for its high aqueous solubility, its flavouring characteristics, and its physico-mechanical properties, which make it suitable for direct compression. Other example :microcrystalline starch and starch. D. Sweetening agents:- Sucralose, aspartame,mannitol, etc. E. Flavouring agents:- Menthol, vanillin, clove oil, etc. F. Backing layer:- Ethyl cellulose, etc. G. Penetration enhancer:- Cyano acrylate, etc. H. Plasticizers:- PEG-100, 400, propylene glycol, etc

Aim and Objective

Aim of The Study:-Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. To improve systems including bypassing hepatic first-pass metabolism, increasing the bioavailability of drugs, improved patient compliance, excellent accessibility,

unidirectional drug flux, and improved barrier permeability compared, for example, to intact skin Objective of The Study:- The buccal region of the oral cavity is an attractive target for administration of the drug of choice. Sustained release formulations have been developed and are gaining in popularity.

1)To increase bioavailability and prevent first pass metabolism of drug. 2)To embed the drug in sustained released buccal patch over period of 6 hour. 3)To provides sustained drug delivery without pre-systemic metabolism.

Methods of preparation
1) Solvent casting:-In this method, all patch excipients including the drug co-dispersed in an organic solvent and coated onto a sheet of release liner. After solvent evaporation a thin layer of the protective backing material is laminated onto the sheet of coated release liner to form a laminate that is die-cut to form patches of the desired size and geometry. 2) Direct milling:-In this, patches are manufactured without the use of solvents. Drug and excipients are mechanically mixed by direct milling or by kneading, usually without the presence of any liquids. After the mixing process, the resultant material is rolled on a release liner until the desired thickness is achieved.

Evaluations of buccal patch

1. Thickness and weight uniformity. 2. Surface ph study. 3. Tensile strength. 4. Content uniformity. 5. Swelling percentage study. 6. Weight increase due to swelling. 7. Area increase due to swelling. 8. Determination of moisture content and moisture absorption. 9. Physical appearance. 10. Surface texture. 11. Weight uniformity. 12. Thickness uniformity. 13. Folding Endurance. 14. Surface pH of films.

References
1)Patel R.S., and Poddar S.S., Development and characterization of mucoadhesive buccal patches of salbutamol sulphate, Curr. Drug Deliv., 2009, 6, 140-144. 2) Chaudhary R., Qureshi MD.S., Patel J., Panigrahi U.P. and Giri IC., Formulation development and in-vitro evaluation of mucoadhesive buccal patches of methotrexate, Inter. J. Pharm. Sci. and Res., 2010, 1(9), 357-365. 3)Deshmane S.V., Channawar M.A., Chandewar A.V., Joshi U.M., and Biyani K.R., Chitosan based sustained release mucoadhesive buccal patches containing verapamil HCL, Inter. J. Pharm. And Pharm. Sci., 2009, 1(1), 216-229. 4)Manasa B., Gudas G.K., Sravanthi N., Madhuri R.A., Lavanya Y., and Pranitha C., Formulation and evaluation of

mucoadhesive buccal patches of resperidone. J Chem. and Pharm. Res., 2010, 2(4), 866-872. 5)Chu D.T., Immunotherapy with chinese medical herbs I. & II, J. Clin. and Lab. Immun., 1988, 25, 119-129.