“FORMULATION AND EVALUATION OF MUCOADHESIVE

MICROSPHERES OFKETOPROFEN”

DISSERTATION PROTOCOL

Submitted to the

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,KARNATAKA,

BANGALORE

BY

SAIKAT MAJUMDAR

M.Pharm, PART- I

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Dr.SUNIL KUMAR AGARWAPh.D

PROFESSOR

DEPARTMENT OF PHARMACEUTICS

Priyadarshini College of Pharmacy,

Koratagere Tumkur- 572121.

2012

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the candidate andaddress / SAIKAT MAJUMDAR
M. Pharm Part-I
Department of Pharmaceutics
PriyadarshiniCollege of Pharmacy
Koratagere Tumkur – 572129
Karnataka.
2. /

Name of the institution

/ PRIYADARSHINI COLLEGE OF PHARMACY
KORATAGERE TUMKUR – 572129
KARNATAKA.
3. /

Course of study & subject

/ Master of Pharmacy inPharmaceutics
4. /

Date of admission to course

/ 15/06/2012
5. /

Title of the topic

“FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF KETOPROFEN”

6. Brief resume of the intended work:

6.1 Need for the study:

Several technical advancements have led to the development of novel drug delivery system that could revolutionize the method of medication and provide number of benefits. Drug delivery systems (DDS) that can precisely control the release rates (or) target drug to a specific body site have had an enormous impact on the health care system. Carrier technology offers an intelligent approach for drug delivery by coupling the drug to a carrier particle such as Microspheres, nanoparticles and liposomes, which modulate the release and absorption characteristics of the drug.1

Microspheres are one of the multiparticulate delivery system and are prepared to obtain controlled the drug release from the dosage form to improve bioavailability, reduces the adverse action and prolong the action of drug, reduce absorption difference in patients, reduce the dosing frequency and adverse effects during prolong treatment. It is needed to formulate in long acting dosage form, reaching to effective biological site rapidly.2

The term mucoadhesion is commonly used to describe an interaction between the mucin layer, which lines the entire GI tract, and a bioadhesive polymer, which could be natural or synthetic in origin.These systems are used to immobilize and localize a drug delivery device in the selected regions of the GI tract, which could be an oral cavity (buccal and sublingual routes).The esophagus, stomach, small intestine or colon(oral cavity).

The various proposed mechanisms of mucoadhesion include lowering of interfacial tension, interpenetration of the mucoadhesive polymer and mucin, formation of an electrical double layer at the adhesive/mucin interface, and formation of a hydrogen bond or van der walls forces of attraction.3

Mucoadhesive microspheres include microparticles and microcapsules of 1-1000 in diameter and consisting either entirely of mucoadhesive polymer or having an outer coating of it, respectively.4

Advantages of microspheres: -

  1. Intimate and prolonged contact of the drug delivery device with the absorbing membrane, which has the potential to maximize both the rate as well as the extent of drug absorption.
  2. Prolonged and controlled GI transit of the dosage forms.
  3. Site specific drug delivery, which has the potential for local (topical) therapy of several conditions, such as a gastric ulcer, esophageal cancer, toothache, and dental sores, as well as potential for the treatment of systemic diseases such as diabetes mellitus and anginapectories.
  4. Taste and odour masking of drug.
  5. Protection of drug against the environment (moisture, light, heat and oxidation.)
  6. To improve the bioavailability.
  7. To decrease the side effects.
  8. To reduce the dose frequency.
  9. To relative stability.
  10. To increase the patient compliance.
  11. To have better therapeutic efficacy.
  12. To reduce the fluctuation in plasma drug concentration.
  13. Safe handling of toxic substances.
  14. Production of sustained release and controlled release medication,5

Among the micro particulate systems, microspheres have a special importance since it is possible to target drug and provide controlled release.6

In this present study aimed to prepare mucoadhesive microspheres containing antiepileptic drug to achieve a controlled drug release profile as well as to increase the gastric transit time.

6.2 Review of Literature:

An explicit literature review was done by exploring through various national & international journals, official standard reference books and by searching through various websites on the internet.

  1. E.Dini et.al, were studied the Synthesis and characterization of cross linked chitosan microspheres containing a hydrophilic drug, Hydroquinone. The microspheres were prepared by suspension cross linking method using glutaraldehyde. It was found that slower drug release rate was obtained from microspheres prepared by using a high concentration of chitosan7.
  1. Anandkumar Shrivastava et.al, were studied the Preparation and characterization of floating microsphere of cemitidine. The cemitidine microsphere were prepared by solvent evaporation method, thus this study shows that floating microspheres will increase the gastric residence time8.
  1. T.Comoglue et.al, haveprepared the microspheres of Pantaprazole by solvent evaporation method and characterize. The pantaprazole is the proton pump inhibitor used in treatment of gastric ulcer and gastroesophagal disease. So purpose of this study was to develop the microspheres that absorb through gastrointestinal tract9.
  1. Hui Yun Zhou et.al, were studied the Preparation of Cellulose acetate (CA) /Chitosan multimicrospheres of Ranitidine. He prepared microsphere by w/o/w emulsion technique. The concentration of CA and the ratio of CA: Chitosan influence the drug release. It prolongs the release of Ranitidine10.
  1. Jain A.K. et.al, Have prepared the Buyont microsphere of Famotidine. The microspheres were prepared by solvent evaporation method. The present study concludes that Buyont microspheres prolongs the gastric residence time of Famotidine11.
  1. Faizi muzaffar,N.Venkatesh Murtyet.al, Were prepared and evaluation of mucoadhesive microspheres of “Amoxicillin Trihydrate by using Eudragit RS 100 and characterization of drug entrapment, cumulative drug release12.

6.3 Objectives of the Study:

The objectives of proposed study are:

1. Preparation of mucoadhesive Microspheres containing Ketoprofen.

2. Evaluation of Microspheres

  • Incorporation efficiency of microspheres.
  • Surface morphology of microspheres.
  • Particle size, shape analysis.
  • In vitro dissolution.
  • Characterization by FT-IR and DSC.
  • Optimized formulations were subjected to stability studies according to ICH Guideline.

7. Materials and Methods:

Materials:-

1)Drug: ketoprofen.

2)Polymers: Hydroxypropyl methylcellulose (HPMC), carbopol934P etc.,

Methods:-

(Any of the below mentioned suitable methods)

  1. Solvent evaporation technique.
  2. Emulsion solvent diffusion method.
  3. Ionic Gelation technique.
  4. Hot melt microencapsulation.

Evaluation: as in section 7.2

7.1 Source of Data:

The preliminary data required for the experimental study was obtained from:

CD-Rom search available at NationalCenter for Scientific Information (NCSI).“Indian Institute of Science, Bangalore”; Dr.H.L.T.College of Pharmacy Library, Scientific abstracts, Journals, Internet sources, relevant books.

The data will be collected by laboratory investigation at Pharmaceutics Department Laboratory of Dr. HLTCP and recording observation. Microspheres will be prepared by using suitable methods.

7.2 Method of collection of data: (Including sampling procedure, if any

Microspheres will be prepared by using suitable methods.

  • The evaluation of microspheres will be carried out by using followingInstruments.
  1. Compatibility studies: - Compatibility of drug with polymers will be investigated using IR.
  2. UV Spectrophotometric (UV-1700 SHIMADZU, JAPAN).
  3. Surface Morphology by SEM.
  4. Optical microscope, Seiveshaker.
  5. Characterization by FT-IR.
  6. Stability chamber.
  • In vitro dissolution study: USP Dissolution Apparatus (DISSO 2000, LAB INDIA)
  • Obtained data will be subjected to statistical analysis.

7.3 Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.

Not applicable.

7.4 Has ethical clearance been obtained from your institution in case of

7.3?

Not applicable.

8. List of References:

  1. K.P.R Chowdary, T.V Narayana and Y.Srinivasa Rao, Preparation and Evaluation of Mucoadhesive Microspheres, theIndianpharmacist, 2006; 5(43):29-34.
  1. A.A. Deshpande, C. T. Rhodes, N. H. Shah and A. W. Malick, Controlled-release drug delivery systems for prolonged gastric residence: an overview, Drug Dev. Ind. Pharm,1996;(22): 531–539.
  1. James Swarbrick, James C.Boylan. Encyclopedia of pharmaceutical Technology.2nd Edn, volume-1 New York, Marcel Dekker, Inc; 2002: PP-896-897.
  1. Mathiowitz E, ChickeringDE, Jacob JS, Mucoadhesive drug delivery system, U.S.Patent, 2001; 6:346.
  1. R. Talukder and R. Fassihi, Gastro retentive delivery systems: a mini review, Drug Dev.Ind.Pharm, 2002; 30:1019-1028.
  1. N. Rouge, J. C. Leroux, E. T. Cole, E. Doelker and P. Buri, Prevention of the sticking tendency of floating minitablets filled into hard gelatin capsules, Eur. J. Biopharm,1997;43: 165–171.
  1. E DINI et.at, Synthesis and Characterization of cross – linked chitosan microspheres for drug delivery application. Journal of Microencapsulation,2003; 3(20): 375-385.
  1. Anand kumar shrivastava Floating microsphere formulation characterization of Cemitidine acta pharm, 2005; 55:277-285.
  1. T.Comoglue.Preparation and development and in vitro evaluation of Pantaprazole loaded microsphere, DrugDelivery, 2008; 5(15): 295-302.
  1. Hui Yun Zhou Cellulose acetate/Chitosan multi microsphere of ranitidine in vitro release Drug Release, 2006; 13:261-267.
  1. A.K.Jain, Buoyant microsphere of famotidine an approach dosage form for gastric dosage form J.young pharm, 2009; 1:20-23.
  1. Faizi Muzaffar, N.Venkatesh Murty, et.al Formulation and Evaluation of Mucoadhesive Microspears of Amoxicillin Trihydrate by using Eudragit RS100. International Journal of Chemtech Research, 2010; 2(1):466-470.
  1. Mona semalty, Shikha Yadav and Ajay semalty, Preparation and Characterization of Gastroretentive Floating Microspheres of Ofloxacin Hydrochloride. International Journal of Pharmaceutical Sciences and Nanotechnology,2010;3(1):819-823.
  1. Venkateswaramurthy N., Sambathkumar R and Perumal P.Preparation and Evaluation of Mucoadhesive Microspheres containing Heparin for Antiulcer Therpy.Research Journal of Pharmaceutical and Technology,2011;4(2):268-270.
  1. P.Vishnu, V.Sai Kishore.Design and development of mucoadhesive microspheres of propranolol hydrochloride.Research journal of pharmaceutical and technology, 2011; 4(1):92-97.
  1. Ashvini Urs .V, Kavitha .K, Mehaboob Y. Design and evaluation of ketoprofen loaded albumin Microspheres,ijps;2011: 910-924.

9. /

Signature of candidate

10. /

Remark of the guide

The above given information is true and this work will be done under my guidance.

11. / Name & Designation of
(in block letters)
11.1 Guide / Dr,SUNIL KUMAR AGARWAL Ph.D
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
PRIYADARSHINICOLLEGE OF PHARMACY KORATAGERE TUMKUR -572129
KARNATAKA.
11.2 Signature
11.3 Co-guide (if any) / --
11.4 Signature / --
11.5 Head of the Department / Dr. SUNIL KUMAR AGARWAL Ph.D
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
PRIYADARSHINICOLLEGE OF PHARMACY
KORATAGERE TUMKUR-572129
KARNATAKA.
11.6 Signature
12. / 12.1Remarks of the Chairman & Principal / The above-mentioned information is correct and I recommend the same for approval.
12.2Signature

1