Formulation and Evaluation of Oral Floating Tablets of Carbonic Anhydrase Inhibitors

“FORMULATION AND EVALUATION OF ORAL FLOATING TABLETS OF CARBONIC ANHYDRASE INHIBITORS”

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BENGALURU, KARNATAKA.

BY

KANALA BRAHMA REDDY.

M.PHARM, PART- I.

DEPARTMENT OF PHARMACEUTICS.

UNDER THE GUIDANCE OF

Mr.D.NARASIMHA REDDY, M.PHARM.

PROFESSOR

DEPARTMENT OF PHARMACEUTICS.

Vivekananda College of Pharmacy,

Dr.Rajkumar Road, Rajajinagar 2nd Stage,

Bengaluru (Dist)-560055.

2010

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE.

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the candidate and address:- /

kanala brahma reddy.

DEPARTMENT OF pharmaceutics,
vivekananda COLLEGE OF PHARMACY, dR.rajkumar road,
rajajinagar 2nd stage,
bengaluru(DIST) - 560055,
KARNATAKA.
2. /

Name of the institution:-

/ vivekananda COLLEGE OF PHARMACY, dR.rajkumar road,
rajajinagar 2nd stage,
bengaluru(DIST) - 560055,
KARNATAKA.
3. /

Course of study & subject:-

/ MASTER OF PHARMACY IN pharmaceutics.
4. /

Date of admission to course:-

/ 29th november 2010
5. /

Title of the topic:-

“FORMULATION AND EVALUATION OF ORAL FLOATING TABLETS OF CARBONIC ANHYDRASE INHIBITORS”
6. /

Brief resume of the intended work:

6.1 Need for the study:

During the last decade, many studies have been performed concerning the sustained release dosage forms of drugs, which have been aimed at the prolongation of gastric emptying time (GET)1.Oral delivery of the drug is by far the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in the formulations2.
FDDS have been developed for drugs that act either locally in the stomach or absorbed from it for these drugs that either poorly soluble at alkaline ph or unstable at intestine or colonic environment3. The gastro retentive drug delivery systems can be retained in the stomach and assist in improving the oral sustained delivery of drugs that have an absorption window in a particular region of the gastrointestinal tract. The formulation containing gas generating agents sodium bicarbonate, calcium carbonate, citric acid or tartaric acid such dosage forms are developed in such a way that, when they come in contact with gastric juice in the stomach, Carbon dioxide is liberated and is trapped in the swollen hydrocolloids. This provides buoyancy to the do-sage form to float over gastric contents4.
Retention systems are important for those drug that are degraded in the intestine like antacids or certain antibiotics, enzymes that act locally in the stomach2. Floating drug delivery system is also called hydro dynamically balanced system or gastro retentive system5. The need for GRDF has led to extensive efforts in both academia and intensity development of such systems these efforts results in GRDF that were designed in large part based on approaches like Bio adhesion to stomach mucous6. The GRDF has applications also for local drug delivery to the stomach and proximal small intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients4.
GRDF are designed on the basis of one of the several approaches like low density dosage forms that remain buoyant over gastric fluid or high density dosage forms reducing motility of GIT tract by concomitant administration of drug or pharmaceutical dosage form. Expanding the dosage form by swelling or unfolding to a large size which limits emptying of dosage form through pyloric sphincter7. To provide good floating behaviour in the stomach, the density of the device should be less than that of the gastric contents (≈1.004 g/cm3)8.
Based on the mechanism of buoyancy, two distinctly different technologies have been utilized in the development of FDDS
1. Effervesent floating drug delivery system
2. Non-effervesent floating drug delivery system.
Effervescent drug delivery systems utilizes matrices prepared with swellable polymers such as methocel or polysaccharides and effervescent components like sodium
bicarbonate and citric or tartaric acid1.
Drug Candidates Suitable for FDDS:
1.  Drugs that have narrow absorption window in GIT (e.g. L-DOPA, paminobenzoic acid, furosemide, riboflavin)9.
2.  Drugs those are locally active in the stomach (e.g. misroprostol, antacids) 10.
3.  Drugs those are unstable in the intestinal or colonic environment (e.g. captopril, ranitidine HCl, metronidazole) 11.
4.  Drugs that disturb normal colonic microbes (e.g. antibiotics used for the
eradication of Helicobacter pylori, such as tetracycline, clarithromycin, amoxicillin) 12.
5.  Drugs that exhibit low solubility at high pH values (e.g.diazepam,chlordiazepoxide, verapamil)13.
Advantages of FDDS: (14,15)
1.  The Floating systems are advantageous for drugs meant for local action in the stomach.
E.g.: Antacids
2.  Acidic substances like aspirin cause irritation on the stomach wall when come in contact with it. Hence FDDS may be useful for the administration of aspirin and other similar drugs.
3.  The Floating systems are advantageous for drugs absorbed through the stomach.
E.g.: Ferrous salts, antacids.
4.  Administration of prolongs release floating dosage forms, tablet or capsules, will result in dissolution of the drug in the gastric fluid. They dissolve in the gastric fluid would be available for absorption in the small intestine after emptying of the stomach contents.
5.  It is therefore expected that a drug will be fully absorbed from floating dosage
forms if it remains in the solution form even at the alkaline pH of the intestine.
Disadvantages of FDDS:16
1.  Floating system is not feasible for those drugs that have solubility or stability problem in G.I tract.
2.  These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently coat, water.
3.  The drugs that are significantly absorbed through out gastrointestinal tract, which undergo significant first pass metabolism, are only desirable candidate.
6.2 Review of Literature:
7. / 1.  V.T.Thakkar, P.A.Shah, T.G.Soni, M.Y. Parma, M.C.Gohel were done fabrication and evaluation of levofloxacin hemihydrate floating tablet using HPMC K4M as polymer. The addition of gel forming polymer (HPMS K4M) and gas generating agent was essential to achieve buoyancy. HPMC K4M (25 mg), gelurice 43/01(%) (15mg) showed controlled drug release and adequate floating properties17.
2.  S.K.Senthilkumar, B.Jaykar, S.Kavimani, were done formulation,characterisation and evaluation of microspheres containing Rabeprazole sodiumwere prepared by solvent evaporation technique using HPMC, MC. It was found that HPMC containing microspheres showed a desirable high drug content, good flow properties, buoyancy and adequate release characteristics hence formulation prepared by using such a polymer are suitable for the development of GRDF18.
3.  Sanjay.S.Patel, S.Ray and R.S.Thakur were done formulation and evaluation of floating drug delivery system containing Clarithromycin for Helicobacter Pylori using HPMC K4M . Among polymers used to improve the gastric residence time, cellulose polymers HPMC K4M, HPMC 15M showed better control over drug release19.
4.  Nirav.S.Sheth was done formulation and evaluation of floating drug delivery system containing HPMC K4M. The formula containing hpmc k4m(150 mg), sodium bicarbonate(100 mg) showed prolonged drug release over(82.56% up to 6hrs) it can be concluded that hydro dynamically balanced tablet of an antibacterial drug clarithromycin can be formulated as approach to increase gastric residence time20.
5.  Sagar Balaso Sangale was done formulation and evaluation of floating felodipine microspheres. Sodium alginate as polymer by solvent eavaparation method. The technique chosen microencapsulation with sodium alginate by solvent evaporation method with temperature change and cross linking with calicium chloride was able to sustain release effectively21.
6.  Vishal.G.Karkhile was done formulation and evaluation of floating tablets of furosemide using HPMC, PEG 6000 by direct compression method. The tablets prepared using HPMC K4M, HPMC K15M and Carbopol formulations evaluated for floating behaviour which showed floating lag time in the range of 126-223 sec and total floating time in the range of 20-24 hrs. The optimized drug formulations showed drug release in a controlled manner for 12 hrs22.
7.  Ziyaur Rahman, Mushir Ali, R.K.Khar were done design and evaluation of bilayer floating tablets of captopril by wet granulation technique using HPMC K4M, HPMC K15M, HPMC K100M, Carbopol 934P, PVP K30. The floating tablets of captopril formulated using HPMC K grade polymer as carrier in vitro studies showed controlled release over 24 hrs23.
6.3 Objective of the study:
The present work is an attempt:
1.  To develop oral Floating tablet contains carbonic anhydrase inhibitors drug by using special excipients like polymers alone or with combinations.
2.  To evaluate for the pre-compression characteristics of powder mixture like bulk density, tap density, angle of repose, cars index, hausners ratio, etc.
3.  To evaluate the post-compression characteristics of the tablet like hardness, friability, thickness, drug content, diameter and water absorption ratio etc.
4.  To carry out in vitro dissolution studies of the tablet formulation.
MATERIALS AND METHODS:
7.1) MATERIALS:
1.Drug: Carbonic Anhydrase Inhibitors
2. Polymers: Graded Polymers
3.Gas Generating Agents
7.2) SOURCE OF DATA
The preliminary data required for the experimental study is obtained from-.
1. CD-Rom search available at National Center for Scientific Information (NCSI), Indian institute of Sciences (IISc), Bengaluru.
2. Journals,
3. Analytical chemistry Books ,
4. Library,
5. Relevant Books,
6. Internet Sources ,
7. Scientific abstracts.
7.3) METHODS:
The floating tablets can be formulated by direct or wet granulation technique.
7.4) METHOD OF COLLECTION OF DATA:
1.  The selected drug shall be characterized and evaluated for its physicochemical properties like solubility and compactability with excipients.
2.  To identify the suitable excipients alone or in combine for further processing.
3.  To carry out pre-formulation studies like bulk density, Tap density, angle of repose, Hausners ratio, compressibility index of the powder mixture (drug and excipients).
4.  To formulate various formulation of the drug containing different ratio of the polymers alone or in combination.
5.  To evaluate the post-compressed tablet for hardness, friability, thickness, tablet diameter, water absorption ratio, content uniformity, in vitro dissolution test, in vitro buoyancy test. etc
7.5) Does the study require any investigation to be conducted on patients/Humans/animals? If so, please describe briefly.
NO
7.6) Has ethical clearance been obtained from your institution in case of 7.3
NOT APPLICABLE
8) LIST OF REFERENCES:
1.  J. Padmavathy, D. Saravanan, D. Rajesh., formulation and evaluation of ofloxacin tablets using HPMC, International journal of pharmacy and pharmaceutical sciences,2011:3(1):170-173.
2.  Anil Kumar J. Shinde, Manojkumar.S., patil and Harinath, Formulation and evaluation of an oral floating tablet of cephalexin, Indian journal of pharmaceutical education and research,2010:44(3).
3.  A.A.Kharia S.N. Harinath, A.K. Singhai., Design and optimization of floating drug delivery of Acyclovir, Indian journal of pharmaceutical sciences,2010:72(5):599-606.
4.  M.Jaimini, A.C. Rana and Y.S. Tanwar., Formulation and evaluation of famotidine floating tablets, Current drug delivery,2007:4:51-55.
5.  Ajay Bagherwal, Dinesh Kumar Patidar., Studies on formulation and evaluation of floating tablets of Ciprofloxacin HCL, International journal of comprehensive pharmacy,5(2):1-4:2010.
6.  S.T. Prajapati, L.D. Patel, D.M. Patel., Studies on formulation and in vitro evaluation of floating matrix tablets of Domeperidone, Indian journal of pharmaceutical sciences,2009:71(1):19-23.
7.  P.G. Yeole, Shagufta Khan, V.F. Patel., Floating drug delivery system need and development,2005:67(3):265-272.
8.  Sunil K Jain, Govind. P. Agrawal, Narendra.K. Jain., Evaluation of porous carrier based floating orlistat microspheres for gastric delivery, AAPS pharmaceutical sciences and technology,2006:7(4):E1-E9.
9.  Garg, R. and Gupta G.D., Progress in controlled gastroretentive delivery systems. Trop J Pharm Res,2008: 7(3): 1055- 1066
10.  Nayak, A.K., Maji, R. and Das, B., Gastroretentive drug delivery systems: a review. Asian J Pharm Clin Res.,.2010: 3(1): 2- 10.
11.  Dave, B. S., Amin, A. F. and Patel M., Gastrorentive drug delivery system of ranitidine HCl formulation and in vitro evaluation. AAPS Pharma Sci Tech.,.2004: 5:1-10.
12.  Hejazi, R. and Amiji, M. , Stomach-specific anti-H. pylori therapy. I: Preparation and characterization of tetracycline of a floating multiple-unit capsule, a high-density loaded chitosan microspheres. Int J Pharm 2002:235: 87-94.
13.  Sawicki, W., Pharmacokinetics of verapamil and nor verapamil from controlled release floating pellets in humans. Eur J Pharm Biopharm.,2001:53: 29-35.
14.  Babu, V. B. M. and Khar, R. K., In vitro and In vivo studies of sustained release floating dosage forms containing salbutamol sulphate. Pharmazie. 45: 268-270. 1990.
15.  Hetal, N. Kikani, A Thesis on, Floating Drug Delivery System, The North Gujarat University, Patan.,2000-2001:11-12
16.  S.Gopal Krishnan, A.Chenthilnathan fddsjournal ph.sci.and .tech ,2011:3(2):548-554.
17.  V.T.Thakkur, P.A.Shah, T.G.Soni, M.Y.Parma., M.L.Gohel,Reseach in pharmaceutical sciences,2008:3(2):65-72.
18.  S.K.Senthilkumar, B.Jaykar, S.Kavimani.,jitps.,2010:1(6):274-282.
19.  Sanjay.S.Patel, S.Ray, and R.S.Thakur,Acta poloniae pharmaceutical drug research,2006:63(1):53-61.
20.  Nirva.S.Sheth, International journal of pharma and bio sciences,2011:2(1):P571-P580.
21.  Sagar Balaso Sangale, International journal of pharmaceutical research and development,2011:3(2):163-170
22.  Vishal.G.Karkhile, International journal of pharmaceutical research and development 2010:1(12):1-9.
23.  Ziyaur Rahman, Mushir Ali, R.K.Khar,Acta pharma,2006:56:49-57.
9. /

Signature of candidate:

10. /

Remark of the guides:

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 / Mr. D.NARASIMHA REDDY M.PHARM.
PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
VIVEKANANDA COLLEGE OF PHARMACY
Dr.RAJKUMAR ROAD,
RAJAJINAGAR 2ND STAGE,
BENGALURU (DIST)-560055.
KARNATAKA.
11.2 Signature:
11.3 Co-guide (if any):
11.4 Signature:
11.5 Head of the Department / Mr. D.NARASIMHA REDDY M.PHARM.
PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
VIVEKANANDA COLLEGE OF PHARMACY
Dr. RAJKUMAR ROAD,
RAJAJINAGAR 2ND STAGE,
BENGALURU (DIST)-560055.
KARNATAKA.
11.6 Signature:
12. / 12.1  Remarks of the Chairman & Principal: / The above-mentioned information is correct and I recommend the same for approval.
12.2 Signature:

From

KANALA BRAHMA REDDY.

M.Pharm, PART I

Dept.Pharmaceutics,

Vivekananda College of Pharmacy,

Dr.Rajkumar road, Rajajinagar 2nd stage.

Bengaluru -560055

TO

The Registrar (Evaluation),

Rajiv Gandhi University of Health Sciences,

Karnataka Bangalore,

4th ‘‘T’’ Block, Jaynagar,

Bangalore-560 041

(Through Proper Channel)

Sub: Submission of Synopsis of Dissertation

Respected Sir,

Herewith, I am submitting synopsis of dissertation work “FORMULATION AND EVALUATION OF ORAL FLOATING TABLETS OF CARBONIC ANHYDRASE INHIBITORS” for registration in M.Pharm (Pharmaceutics) of Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka.