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. CO-SUPERVISOR.

DR. (PROF)VINEY CHAWLA ASST.PROFESSOR

G.I.S.I.P.S .DEHRADUN 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 SurveyPatel 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 40°C 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)

Systematic (IUPAC) nameN,N-Dimethylimidodicarbonimidi diamide

Clinical dataTrade names Glucophage, Etform

AHFS/Drugs.com FDA Professional Drug Information

Medline Plus a696005Licence data US FDA linkPregnancy cat C (AU) B (US)

FormulaMol. mass

C4H11N5129.16364

Routes oral

Pharmacokinetic data

Bioavailability 50–60%

Protein binding Minimal

Metabolism Not by liver

Half-life 4-8.7 hours

Excretion 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 50–60% 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 ProfileActive 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 preparation1) 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 patch1. 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.

References1)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.