“FORMULATION AND EVALUATION OF COLONTARGETED DRUG DELIVERY SYSTEM FOR

ANANTI-AMOEBIC DRUG”

DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCE

BANGALORE, KARNATAKA.

BY

SANDEEP KUMAR SINGH

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

MR. VAZIR ASHFAQ AHMED

ASST. PROFESSOR

DEPARTMENT OF PHARMACEUTICS

M.M.UCollege Of Pharmacy

Ramnagaram-571511.

Karnataka

2010

RAJIV GANDHI UNIVESITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) /

SANDEEP KUMAR SINGH.

DEPARTMENT OF pharmaceutics,
M.M.U.COLLEGE OF PHARMACY,
K.K. DODDI, RAMDEVARA BETTA ROAD,RAMANAGARA-571511.
KARNATAKA.
2. / NAME OF THE INSTITUTION / M.M.UCOLLEGE OF PHARMACY
K.K DODDI, RAMADEVERA BETTA ROAD,RAMANAGARAM-571511
KARNATAKA.
3. /

COURSE OF STUDY AND SUBJECT

/ M. PHARM
PHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / 15th JUN 2010
5. /

TITLE OF TOPIC

/ “FORMULATION AND EVALUATION OF COLON TARGETED DRUG DELIVERY SYSTEM FOR AN
ANTI-AMOEBIC DRUG”
6. / BRIEF RESUME OF THE
INTENDED WORK
6.1 Need for the study
6.2 Review of the literature
6.3 Objectives of the study / ENCLOSURE-I
ENCLOSURE-II
ENCLOSURE-III
7. /

MATERIALS AND METHODS

7.1 Source of data
7.2 Method of collection of data
7.3 Does study require any Investigations or interventions to be conducted on patients or Other human or animal? If so, Please describe briefly.
7.4 Has ethical clearance been obtained from your institution in case of 7.3 / ENCLOSURE-IV
ENCLOSURE-V
ENCLOSURE-VI
ENCLOSURE-VI
8. / LIST OF REFERENCES / ENCLOSURE-VII
9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF GUIDE / FORWARDED FOR APPROVAL
NAME AND DESIGNATION OF
11.1 Guide
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department
11.6 Signature / MR. VAZIR ASHFAQ AHMED
ASST. PROFESSOR
M.M.UCOLLEGE OF PHARMACY
K.K DODDI, RAMADEVERA BETTA ROAD,RAMANAGARAM-571511
KARNATAKA
Not applicable
Not applicable
VAZIR ASHFAQ AHAMED
ASST.PROFESSOR
DEPARTMENT OF PHARMACEUTICS,
M.M.UCOLLEGE OF PHARMACY
K.K DODDI, RAMADEVERA BETTA ROAD,RAMANAGARAM-571511
KARNATAKA
12. / 12.1 Remarks of the
Chairman and principal
12.2 Signature / SUBMITTED FOR APPROVAL
BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I

6.1 Need for the study:

Large intestine is susceptible to many diseases including irritable bowel syndrome, intestinal amoebiasis, constipation, crohn’s disease, ulcerative colitis, carcinomas and infections etc.
At present these disease are often poorly and inefficiently managed either by oral route,in which oral drugs are largely absorbed before they reach the colon or by rectal route of administration which is less acceptable.
Amoebiasis is a large intestinal infection caused by Entamoeba histolytica. The drugs should reach the colon for effective treatment of intestinal amoebiasis. Tinidazole, Metronidazole and Ciprofloxacin are generally used as anti-amoebic drugs.
The conventional tablet dosage form provides minimal amount of the drug in the colon with undesirable adverse effects due to variation in the transit time.
The drugs are targeted directly to the site of action in the colon, by this treatment will be effective. Better treatment may be possible with a minimum dose of the drug.
Time dependent system, pH dependent system, microbiologically controlled system, multiparticulate system and luminal pressure controlled system are the latest approaches of drug delivery to the colon.
Development of once a day, sustained release multiparticulate formulation of an anti-amoebic drug decreases the adverse effects, cost of treatments and enhances patient compliance.
Using natural polymers as a coating agent, biocompatibility and biodegradability of multiparticulate formulation can be enhanced.
In the present study an attempt is undertaken to develop multiparticulate drug delivery of a model anti-amoebic drug for better treatment of amoebiasis and other protozoal infections, with reduced side effects and better patient compliance.
-
ENCLOSURE II
6.2Review of literature:
  1. Zahirulkhan, Zeljkopreeg, Navena Kurjakoviee., have formulated pH dependent colon targeted oral drug delivery system using methacrylic acid polymers.The coated tablets were tested for in-vitro for their suitability for pH dependent colon targeted oral drug delivery.
  1. Fatemeh Atyabi, Rudabeh Vahabzadeh, Rassoul Dinarvand., have prepared ethyl cellulose coated gelatin microspheres as a multiparticulate colonic delivery system for 5-aminosalicilic acid. By solvent evaporation method were prepared gelatin microspheres containing 5-aminosalicylic acid and the prepared microspheres were then coated with ethyl cellulose using a coacervation-phase separation technique. It was shown that this system could provide a suitable drug release pattern for colonic delivery of active agents,
  1. Lee F. Siew, Abdul W. Basit, J. Michael Newton., The purpose of the study was to establish the physico-mechanical and digestibility properties of water-miscible organic solvent-based amylase ethylcellulose films as potential coatings for colonic drug delivery. The results suggested that amylase ethyl cellulose films could be used as coatings for colonic drug delivery.
  1. Rana Mazumder,et al.,have studied formulation and in vitro evaluation of natural polymers based microspheres for colonic drug delivery. The prepared MTZ microspheres by ionotropic gelation technique were characterized by entrapment efficiency, particle size, micromaritic properties, in vitro release behavior,scanning electron microscopy,fourier transforms infrared spectroscopy.
  1. Marta Rodriguez, Jose Vila Jato., have designed a new multiparticulate dosage form consisting of a hydrophobic core coated with a pH dependent polymer for colonic drug delivery. The system consisted of drug loaded cellulose butyrate microspheres coated with an enteric polymer Eudragit.
  1. S. Lakshmana Prabu,et al.,it was suggested the formulation and evaluation of oral sustained release of Diltiazem Hydrochloride using rosin as matrix forming material. Rosin is a natural resin used as a hydrophobic matrix material for the controlled release, using diltizem HCL. Matrix tablets were prepared by direct compression method using rosin as matrix forming material in different ratio. The rosin is useful in developing sustained release matrix tablets, it prolongs the release of water soluble drug up to 24h.
  1. Y.S.R. Krishnaiah, P.R. Bhaskar Reddy, V. Satyanarayana.R.S. Karthikeyan., have developed oral colon targeted drug delivery systems for metronidazole using guar gum as a carrier. Matrix, multilayer and compression coated tablets of metronidazole containing various proportions of guar gum were prepared.The results of the study showed that coated metronidazole tablets with guar gum of metronidazole for local action in the colon was more effective.
  1. Ziyaur Rahman, Kanchi Kohli, Roop K Kaur, Areeg A.A Shamsheer.,Core microspheres of alginate with 5-fluorouracil were prepared by modified emulsification method in liquid paraffin followed by cross linking with calcium chloride. These core microspheres were coated with Eudragit s-100 by solvent evaporation technique. Drug release was sustained for up to 20 hours in formulations with core microspheres to Eudragit coat ratio of 1:7 and no change in size, shape and drug content were observed.
  1. H.N.Shivakumar, Sarasija Suresh, B.G.Desai., it was suggested the design and evaluation of pH sensitive multiparticulate system for chronotherapeutic delivery of diltiazepam hydrochloride. A pH sensitive multiparticulate system intended to approximate the chronobiology of angina pectoris is suggested for colon targeting. Core pellets was coated with microcrystalline cellulose and further coating of pellets using Eudragit S -100. In-vitro dissolution studies of the coated pellets were performed following pH progression method. the drug release from the coated pellets depends on the coat weights and pH of the dissolution media.
  1. M L Soni, M Kumarand K P Namdeo.,have studied Sodium alginate microspheres for extending drug release. They have preparedspherical microspheres of theophylline (TP) using sodium alginate as the hydrophilic carrier for prolong drug release. The shape, surface and size characteristics were determined by scanning electron microscopy.
  1. Sunil K. Jain,Gopal Rai,D. K. Saraf, and G.P.Agrawal.,have studied preparation and Evaluation of Albendazole Microspheres for Colonic Delivery. Microspheres of Eudragit RL has developed for delivery of albendazole into the colon.The effects of polymer concentration, stirring rate, and concentration of emulsifier on particle size and drug loading has suggested.
ENCLOSURE-III
6.3Objectives of the study
The present work is an attempt to,
To prepare and characterise microspheres of an anti-amoebic drug for
colonic drug delivery.
To prepare and characterise double layered multiparticulates using water insoluble polymers as carrier.
Evaluation of prepared formulation consist of
  1. Physical characterisation
  2. Drug entrapment efficiency, drug content uniformity
  3. In-vitro release studies
  4. Micromeritic properties of coated microspheres
MATERIALS AND METHODS:
Materials:
Drugs:Anti-amoebic drug (Any one which is available).
Polymers: Ethylcellulose, Eudragit, Rosin, Gelatin, alginate etc.
Equipments:Analytical balance, Stability chamber, Dissolution apparatus, UV – Spectrophotometer,fourier transforms infrared spectroscopy,Magnetic Stirrer, pH Meteretc.
Methods:
Preparation of microsphere by one of the following methods
Single emulsion technique,
Double emulsion technique,
Polymerization techniques,
Phase separation coacervation technique,
Spray drying and spray congealing,
Solvent evaporation.
ENCLOSURE-IV
7.1. Source of Data
The preliminary data required for the experimental study is obtained from
CD-Rom search available at NationalCenter for Scientific Information (NCSI), Indian institute of Sciences (IISc), Bangalore.
Journals,
Library,
Relevant Books,
Internet Sources,
Analytical chemistry Books ,
Scientific abstracts.
ENCLOSURE-V
7.2. Method of Collection of Data
The data will be collected from the prepared formulation, after subjecting the formulation to different evaluation parameters like, Physical characteristics, Drug entrapment efficiency, Invitro release studies, Micromeritic properties of coated microspheres etc.
ENCLOSURE-VI
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.
-NO-
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
-NOT APPLICABLE-
ENCLOSURE-VII
LIST OF REFERENCES
  1. Zahirulkhan, Zeljkopreeg, Navena Kurjakoviee., pH dependent colon targeted oral drug delivery system sing methacrylic acid polymers. J. Control. Rel. 1999; 58: 215-222.
  2. Fatemeh Atyabi, Rudabeh Vahabzadeh, Rassoul Dinarvand., Preparation of Ethyl cellulose Coated Gelatin Microspheres as a Multiparticulate Colonic Delivery System for 5-Aminosalicilic Acid. Ira. J. Pharm. Res. 2004; 2: 81-86.
  3. Lee F. Siew, Abdul W. Basit, J. Michael Newton., The properties of amylose–ethylcellulose films cast from organic-based solvents as potential coatings for colonic drug delivery. Eur. J. Pharm. Sci 2000; 11: 133-139.
  4. Rana Mazumder, et al., Formulation and in vitro evaluation of natural polymers based microspheres for colonic drug delivery. Int. J. Pharm. and Pharm. Sci.,Vol 2, 2010
  5. Marta Rodriguez, Jose Vila Jato., design of a new multiparticulate dosage form consisting of a hydrophobic core coated with a ph dependent polymer for colonic drug delivery. J. Control. Rel. 1998; 55: 67-77.
  6. S. Lakshmana Prabu, et al., Formulation and evaluation of oral sustained release of Diltiazem Hydrochloride using rosin as matrix forming material. Ars Pharm., 2009, Vol.50; 32-42.
  7. Y.S.R. Krishnaiah, P.R. Bhaskar Reddy, V. Satyanarayana, R.S, Karthikeyan., Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis. Int. J. Pharm.2002; 236: 43-55.
  8. Ziyaur Rahman, Kanchi Kohli, Roop K Kaur, Areeg A.A Shamsheer., Characterisation of 5-Fluorouracil microspheres for colonic drug delivery.AAPS Pharm. Sci. Tech.2006; 7(2): E1-E9.
  9. H.N.Shivakumar, Sarasija Suresh, B.G.Desai., design and evaluation of ph sensitive multiparticulate system for chronotherapeutic delivery of diltiazepam hydrochloride. Ind. J. Pharm. Sci 2006; 68(6): 781-787..
  10. M L Soni, M Kumar and K P Namdeo.,Sodium alginate microspheres for extending drug release. Int. J. of Drug Delivery, 2 (2010) 64-68.
  11. Sunil K. Jain, Gopal Rai, D. K. Saraf, and G.P.Agrawal., The Preparation and Evaluation of Albendazole Microspheres for Colonic Delivery. Pharm. Tech.Dec. 2004