FORMULATION AND EVALUATION OF COLON TARGETED TABLETS OF ORNIDAZOLE FOR THE TREATMENT OF AMOEBIASIS
M. Pharm Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore– 560 041
By
Mr. PRAGNESH PATEL B.Pharm
Under the Guidance of
Mr. ANUPKUMAR ROY M.Pharm
Assistant professor
Department of Industrial pharmacy,
Acharya & B.M.Reddy College of Pharmacy,
Soldevanahalli, Chikkabanavara (Post)
Hesaraghatta Main Road, Bangalore – 560 090.
2008-2009
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1 / Name of the candidate and address /mr.PRAGNESH PATEL
At&post-Goral,Ta-Idar,
Dist-Sabarkantha,
Gujarat, 383 410.
2 / Name of the Institution / Acharya & B.M. Reddy college of pharmacy,
Chikkabanavara post ,
Hesaraghatta Main Road , Soldevanahalli,
Bangalore-560 090.
3 / Course of the study and subject / M. Pharmacy
(Industrial Pharmacy)
4 / Date of admission / 25/05/2008
5 / Title of the project :-
FORMULATION AND EVALUATION OF COLON TARGETED TABLETS OF ORNIDAZOLE FOR THE TREATMENT OF AMOEBIASIS
6
6.1 / BRIEF RESUME OF INTENDED WORK :-
Need for the study:-
Oral delivery of drugs to the colon is valuable in the treatment of diseases of colon (ulcerative colitis, crohn’s disease, carcinomas and infections) whereby high local concentration can be achieved while minimizing side effects that occur because of release of drugs in the upper GIT or unnecessary systemic absorption. The colon is attracting interest as a site where poorly absorbed drug molecule may have an improved bioavailability. This region of the colon is recognized as having a somewhat less hostile environment with less diversity and intensity of enzymatic activity than the stomach and small intestine. Additionally, the colon has a longer retention time and appears highly responsive to agents that enhance the absorption of poorly absorbed drugs.
The simplest method for targeting of drugs to the colon is to obtain slower release rates or longer release periods by the application of thicker layers of conventional enteric coatings or extremely slow releasing compress coated tablets.2
Ornidazole is antiamoebic drug useful in infection caused by the protozoa entamoeba histolytica. it’s plasma half life is 12-14 hrs. ornidazole is selectively toxic to anaerobic microorganisms. After entering the cell by diffusion its nitro group is reduced by certain redox proteins operative only in anaerobic microbes to highly reactive nitro radical which exerts cytotoxicity by damaging DNA and other critical biomolecules.12
Advantage of colon targeted drug delivery3
v Delivering the drug to its target site can reduces toxicity and harmful systemic effects of a drug.
v Toxicity can be reduced by administrating the drug in a non-toxic form (prodrug)that gets activated in the target site.
v The dose of the drug can be reduced to achieve the desire effects.
v Avoidance of hepatic first pass metabolism.
v Enhancement of the absorption of large molecule such as proteins & peptides.
So in order to achieve above advantages, in the present study ornidazole tablet has been used to target colon for the treatment of amoebiasis.
6.2 / REVIEW OF LITERATURE :-
They have reported a comparative in vitro evaluation using different enteric coated polymer viz. eudragit, a cellulose acetate phthalate with shellac and ethyl cellulose, as carrier for colon specific drug delivery. Lactose based indomethacin tablet were prepared. These coated formulations were evaluated for dissolution rates under simulated stomach and small intestine condition. From the dissolution data obtained, it was found that the dissolution rate varied with the type and concentration of polymer and coat thickness used, a 3% coat of shellac was most suitable for colonic drug delivery.5
They have developed colon targeted drug delivery system for albendazole using gaur gum as a carrier. Matrix tablet containing various proportion of gaur gum were prepared by wet granulation technique using starch as a binder. All the formulations were subjected to in vitro drug release studies. The result shows that matrix tablet containing either 10% and 20% of gaur gum are most likely to provide targeting of albendazole for local action in colon.7
They have proposed the pharmaceutical approaches to colon targeted drug delivery system. In this study they have mention the various strategies for targeting orally administered drug to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymer, formulation of timed release system, exploitation of carriers that are degraded specifically by colonic bacteria, bioadhesive system and osmotic controlled drug delivery system.1
They have demonstrated the in vitro evaluation of dissolution behavior for colon-specific drug delivery system in multi-pH media using united states pharmacopoeia apparatus II and III. The tablet was prepared using acetaminophen. Each tablet consisted of
approximately 20% acetaminophen, 78% lactose and 25% HPMC. The dissolution testing was carried out on USP dissolution apparatus II and III in buffers-artificial gastric fluid (pH 1.2), artificial intestinal fluid (pH 6.8).11
They have used and examined pectin for colonic delivery of drug. Pectin is intact in the upper GIT and degraded by colonic bacteria. The study include gelation of pectin, calcium cross-linked pectinate, composite of pectin and other polymers, technologies to fabricate pectin into useful drug delivery vehicles, and methods to evaluate release kinetics of incorporated drug.10
They have developed the colon targeted drug delivery system for mebendazole using guar gum, were prepared by wet granulation technique using starch paste. The experimental studies reveals that gaur gum matrix tablet released 8-15% of the mebendazole in the physiological environment of stomach and small intestine but when the dissolution study was continued in simulated colonic fluids tablet containing 20% of gaur gum released 83% of mebendazole in colon.4
They have evaluated a guar gum as a compression coat for targeting to colon, the in-vitro drug release studies have shown that guar gum in the form of compression coat applied over indomethacin core tablet protect the drug from being released under condition mimicking mouth to colon transit. Studies in pH 6.8 phosphate buffered saline (PBS) containing 4% w/v rat caecal contents have demonstrated the susceptibility of guar gum to the colonic bacterial enzyme action with consequent drug release.9
They have demonstrated the in vitro drug release studied on gaur gum–based colon targeted drug delivery system of 5-fluorouracil. Fast disintegration tablet were compression
coated with 60, 70, and 80% of gaur gum. The result of studies showed that the compression coated tablet containing 80% of gaur gum was most likely to provide targeting of 5-fluorouracil.8
They have reported the potential of organic based ethylcellulose film coating as oral colonic specific drug delivery system using 5-aminosalicylic acid as drug which was coated with ethylcellulose as polymer. The dissolution study was carried out, after collecting the dissolution data, the data suggest that the rate of release was inversely proportional to the thickness of the coat, implying that the film coat was controlling the release process.6
6.3 / OBJECTIVES
The objective of the present study is to formulate colon targeted compression coated tablets containing ornidazole, which would protect the release of the drug in the physiological environment of the stomach and small intestine and release the drug in the colon providing local action for the treatment of the amoebiasis. The major objectives of the present work are:
1. To develop and formulate compression coated ornidazole tablets for drug release in the colon.
2. To carry out statistical optimization and find out optimized formulations for various polymer combinations.
3. To carry out preformulation studies for possible drug/polymer/excipients interactions by FT-IR/DSC.
4. To develop analytical method for the estimation of the drug in the formulation.
5. To evaluate the core and the compression coated tablets for the following parameters:
a. Diameter and Thickness.
b. Hardness and Friability.
c. Weight uniformity.
d. Content uniformity.
e. In- vitro drug release studies.
6. To carry out short term stability studies on the most satisfactory formulation as per ICH guidelines.
7
7.1
/ MATERIALS & METHODS:-SOURCE OF DATA: -
1) Review of literature from:a) Journal such as
i) Indian Journal of Pharmaceutical Sciences
ii) European Journal of Pharmaceutical Sciences
iii) Journal of Controlled Release
iv) International Journal of Pharmaceutical Sciences
v) Drug Development and Industrial Pharmacy
vi) Indian Drugs
b) World Wide Web.
c) I.I.Sc Library, Bangalore.
d) J-Gate@Helinet
2) Laboratory based studies.
7.2 / METHODS OF COLLECTION OF DATA:-.
1) To carry out preformulation study
A. Drug polymer interaction
B. Micromeritic study
a) Angle of repose
b) Bulk density
c) Percentage compressibility
2) To develop and formulate compression coated tablets by direct compression/wet granulation methods using various polymers.
3) Evaluation of the various properties of the formulated compression coated tablets:-
a) Physical properties:-
· Diameter and Thickness
· Hardness and Friability
· Uniformity of Weight and Content
b) In vitro dissolution studies will be carried out in a USP Type-II dissolution apparatus containing Simulated Gastric Fluid (pH-1.2 in stomach for 2 hours; pH 6.8 in small intestine for 3 hours;)
4) To carry out short term stability studies on the most satisfactory formulation as per ICH guidelines at 30 ± 20C (65 ± 5 %RH) and 40 ± 20C (75 ± 5 %RH).
1.
7.3 / Does the study require any investigation or investigation to be conducted on patient or other humans or animals?
“NO”
7.4 / Has ethical clearance been obtained from your institution in case of 7.3?
“NOT APPLICABLE”
8 / LIST OF REFERENCES:-1. Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery system.Indian J Pharm Sci 2003; 6(1):33-66.
2. Jain NK. Advances in controlled and novel drug delivery. delhi CBS publishers and distributors. 2000;89-119.
3. Dr Abdul Basit and John Bloor. Perspectives on Colonic Drug Delivery. Business Briefing : Pharmatech 2003;1-5.
4. Krishnaiah YSR, Veer Raju P, Dinesh Kumar B, Bhaskar P, Satyanarayana V. Development of colon targeted drug delivery drug system for mebendazole. Journal of Controlled Release 2001;77:87-95.
5. Sinha VR, Kumaria R. Coating polymer for colon specific drug delivery: a comparative in vitro evaluation. Acta Pharma 2003;53:41-7.
6. Siew LF, Basit AW, Newton JM. The potential of organic-based amylase-ethylcellulose film coatings as oral colon-specific drug delivery system. AAPS Pharm Sci Tech 2000;1(3):22.
7. Krishanaiah YSR, Rao Latha Nageshwara, Karthikeyan RS, Bhaskar P and Satyanarayana P. Development of colon targeted oral gaur gum matrix tablet of albendzole for the treatment of helminthiasis. Indian J Pharm Sci 2003; 65(4): 378-85.
8. Krishnaiaha YSR, Satyanarayana V, Dinesh kumar B, Karthikeyan RS. In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil. European J Pharm Sci 2002;16:185–92.
9. Krishnaiah YSR, Satyanarayana S, Rama Prasad YV. Evaluation of guar gum.International J Pharm Sci 1998;177:137–46.
10. LinShu Liu, Marshall L Fishman, Joseph Kost, Kevin BH. Pectin-based systems for colon-specific drugdelivery via oral route. Biomaterials 2003;24:3333-43.
11. Jinhe Li, Libo Yang, Sheila M Ferguson, Tom J Hudson. In vitro evaluation of dissolution behavior for a colon-specific drug delivery system (CODESTM) in multi-pH media using United States pharmacopeia apparatus II and III. AAPS Pharm Sci Tech 2002;3(4): 33.
12. Tripathi KD. Essentials of medical pharmacology. New delhi: JAYPEE brothers medical publishers 2003;5:749-58.
9 / Signature of the candidate:
10 / Remarks of the Guide:
11 / Name and Designation of:
11.1 Institutional Guide: / Mr. ANUP KUMAR ROY
Assistant professor
Dept. of Industrial Pharmacy
Acharya & B.M.Reddy College of Pharmacy,
Chikkabanavara Post, Hesaraghatta Main Road,
Soldevanahalli, Bangalore-560 090.
11.2 Signature:
11.3 Co-Guide: / Mr.VENKATESH D.P.
Lecturer
Dept. of Industrial Pharmacy
Acharya & B.M.Reddy College of Pharmacy,
Chikkabanavara Post, Hesaraghatta Main Road,
Soldevanahalli, Bangalore-560 090.
11.4 Signature:
11.5 Head of the Department: / Dr. ROOPA KARKI
Professor & HOD
Dept. Of Industrial Pharmacy
Acharya & B.M.Reddy College of Pharmacy,
Chikkabanavara Post, Hesaraghatta Main Road,
Soldevanahalli, Bangalore-560 090.
11.6 Signature
12 / 12.1 Remarks of the Principal
12.2 Signature /
Dr. DIVAKAR GOLI
Principal
Acharya & B.M.Reddy College of Pharmacy, Chikkabanavara Post Hesaraghatta Main Road, Soldevanahalli, Bangalore-560 090.2