FORMULATION AND EVALUATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEM OF RAMIPRIL

M. PHARM. DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE.

By

PATEL SALEEM ABDUL KARIM

B.Pharm

Under the guidance of

DR. SATYANANDAM S

M.pharm.,Ph.D

Professor

DEPARTMENT OF PHARMACEUTICS

LUQMAN COLLEGE OF PHARMACY, GULBARGA

2013-14

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate & Address
(In block letters) / : / PATEL SALEEM ABDUL KARIM
LUQMAN COLLEGE OF PHARMACY
P&T Colony, Old Jewargi Road,
GULBARGA-585 102. KARNATAKA STATE
2. / Name of the Institution / : / LUQMAN COLLEGE OF PHARMACY
P&T Colony, Old Jewargi Road,
GULBARGA-585 102. KARNATAKA STATE
3. / Course of Study and Subject / : / M.PHARM. (PHARMACEUTICS)
4. / Date of Admission to Course / : / 09-01-2013
5. / Title of the Topic / : / FORMULATION AND EVALUATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEM OF RAMIPRIL
6.
/ Brief resume of the intended work
6.1 Need for the study:
It is widely known that gastric residence time (GRT) is one of the important factors affecting the drug bioavailability of pharmaceutical dosage form. Variable and short gastric emptying time can result in incomplete drug release from drug delivery system (DDS) above the absorption zone (stomach or upper part of small intestine), leading todiminished efficacy of administered dose. Floating drug delivery system (FDDS) is one of gastro retentive dosage form which could prolonged gastric residence timeto obtain sufficient drug bioavailability The system basically float in the gastric fluid because of its lower bulk density compared to that of aqueous medium.1
Various approaches for preparation of gastroretentive drug delivery system include floating systems, swellable and expandable systems, high density systems, bioadhesive systems, altered shape systems, gel forming solution or suspension system and sachet systems. Among these, the floating dosage form has been used most commonly. The floating systems include gas-generating systems, noneffervescent systems and raft forming systems.
Ramipril an angiotensin-converting enzyme inhibitor. The drug is freely soluble and has elimination half life after an oral dose of 2-4 hours.It is stable at pH 1.2 and as pH increases the drug becomes unstable and undergoes a degradation reaction.2Ramipril belongs to the class angiotensin converting enzyme inhibitor (ACE inhibitor). It affects renin angiotensin system and inhibits the conversion of relatively inactive angiotensive I to active angiotensin II.3Ramipril may be used in the treatment of hypertension, congestive heart failure, nephropathy, and to reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events..4
The present study onRamipril in the form of gastrorentive tablet will provides a combination of spatial and temporal control of drug delivery to patientsfor effective therapeutic results5,6
6.2Review of Literature:
Literature survey was carried out on the proposed research work by referring various scientific research journals, internet and Helinet facilities, no work has been reported on the proposed research topic and few articles related to the topic are listed below.
  1. Ganagadharappa HV etal7. Gastric floating drug delivery systems- A review to develop an efficient floating drug delivery systems for the drug having narrow absorption window, unstable at higher pH value and drugs have local effect may benefit from developing floating drug delivery systems to develop the perfect systems that will be retain in stomach for a long time using effervescent and non effervescent floating drug delivery system.
  2. Tamizharasi Setal8. Formulation and Evaluation of Floating Drug delivery system of Aceclofenac is reported. In rhis a sustained release system for Aceclofenac design to increase its residence time in stomach without contact with mucosa was achived through the preparation of floating microspheres by the emulsion solvent diffusion technique.
  3. Dhole RAetal9.Design and evaluate floating microcarriers of Ramipril by using polymers like sodium alginate along with HPMC and ethyl cellulose by lonotropic gelatin technique. Present study involves the preparation and evaluation of floating microcarriers of Ramipril as model drug for prolongation of gastric residence time.
  1. Raghavendra Rao NG et al10.Prepared gas power tablets containing Cefixime by direct compression method to increase the gastric retention time using different concentration of hydrophilic polymers were they concluded that, the prepared formulation retained for longer periods of time in the stomach (spatial control) and provide controlled release of drug.
  1. Gambhire MN et al11.Oral floating matrix tablet formulation of diltiazem hydrochloride was reported. A32 factorial design was applied to systematically optimize the drug release profile. A high level of both method K100 and campritol 888favors the preparation of floating control release of diltiazem HCL tablets.
  1. Jaimini Met al12. Have prepared famotidine floating tablet by effervescent technique using two different grade of methocel K100 and methocel K15M from this study they concluded that tablet with methocel K100 were found to float for longer duration as compared with formulation containing methocel K15M.

6.3Objectives of the Study:
The study will plan with following objectives.
Generates and entraps a gas in a hydrated matrix upon contact with an aqueous medium or gastric fluids, and which retains a substantially monolithic form in the stomach.
Provides increased gastric residence time and there by a longer period of the drug delivery system in GI tract.
Delivers the drug at controlled rate such that the drug is delivered over period of time.
It gives constant blood levels of the active ingredient as compared to uncontrolled fluctuations observed when multiple dosage of quick releasing conventional dosage form are administered to a patient.
It reduces the frequency of dosing and may also reduce the severity and frequency of side effects.
7. / Material And Methods
7.1 / Materials
Drugs: RAMIPRIL
Viscolyzing agent: Guar Gum/xanthan gum,HPMCetc.
Swelling agent: Cross-linked polyvinyl pyrrolidone etc.
Gel forming polymer: Sodium alginate etc.
Gas Generating Components:Calcium carbonate or bicarbonates
7.2 / Methods:
Preparation of Ramipril Gas Powered Systems 10:
The gas powered systems of Ramiprilwill be preparedby direct compression or wet granulation method.
Evaluation of Ramipril Gas Powered systems for Controlled release14:
The prepared gas powered system for controlled release will be evaluated for
Weight variation
Hardness (tablets)
Friability (tablets)
In-vitro dissolution study
Drug content
In-vitro buoyancy time
Drug release profile and
Drug Excipient interaction.
Stability studies
7.3 / Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so please describe briefly.
------Not under the plan of the work ------
7.4 / Has ethical clearance been obtained from your institution in case of 7.3
------Not applicable------
8. / List of References:
  1. Meka L, Kesavan B, Chinnala KM, Vobalaboina V,and Yamsani MR.“Preparation of Matrix type Multiple-unit Gastroretentive Floating Drug Delivery system for Ramipril based on the gas formation technique”. AAPS PharmaScis Tech, 2008 June ; 9(2): 612-619.
  2. Mehta TJ, Motihal M, Patel MR, Patel KR,Alpesh D Patel, and Patel NM. “Innovation on Development and Evaluation of Gastric Oral Floating Capsule Containing Ramipril”. Der Pharmacia Lettre, 2011; 3(3): 103-109.
  3. Vijaysankar GR,Naveen Kumar Jakki S,Suresh AG, Packialakshmi M.“Formulation and Evaluation of RamiprilGastroretentiveFloating Drug Delivery System”. Int. J.Pharm and Ind. Res, Jan-March 2011,1 (1): 11-16.
  4. Naresh T, Hemadri S, Stainforth, John N. “Orally Administered Drug Delivery System Providing Temporal and Spatial Control” 1998.
  5. Garg S, and Sharma S.“Gastro Retentive Drug Delivery Systems”. PharmTech, 2003, 160-166 pp.
  6. Ganagadharappa HV, Pramod Kumar TM, and Shivakumar HG. “Gastric floating drug delivery system”. a review, IJPER, 2007 : 41 (4).
  7. Tamizharasi S, Shivakumar T, Chandra RJ.”Formulation and evaluation of floating drug delivery system of Aceclofenac”. Int.J.Drug DS 2011, 3(3): 242-251.
  8. Dhole AR, Gaikwad PD, Bankar VH, Pawar SP.“Design and Evaluation of Floating Microcarriers of Ramipril”. IJPS, 2011, 8(2) :124-129.
  9. Raghavendra Rao NG, Pentewar R., Bussetti SS. Formulation and Evaluation of Gas Powered systems of Cefixime Tablets for controlled release”. Int J Pharma Bio Sci 2010;1(2):1-15.
  10. Gambhire MN, Ambade KW, Kurmi DS, Kadam UJ, andJadhav KR.“Development and in-vitro evaluation of an oral floating matrix tablet formulation of diltiazemhydrochloride”. AAPS Pharm Sci Tec., 8(3), EI-9.
  11. Jaimini M, Rana AC.“Tanwar. Formulation and Evaluation of Famotidine Floating Tablets’’. Current Drug Del 2007, 4(1): 51-4.
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9. / Signature of Candidate / PATEL SALEEM ABDUL KARIM
10. / Remarks of the Guide / The Proposed Research topic is selected with a hope that, it may improve the therapeutic efficacy of the drug by increased G.I retention time and by controlled release. So, recommended for registration.
11. / Name and Designation of
(in block letters)
11.1 / Guide /

DR. SATYANANDAM S

Professor
department of Pharmaceutics.
Luqmancollege of Pharmacy,
Gulbarga.
11.2 / Signature of Guide
11.3 / Co-guide / M.A.SALEEM
Asst. Professor
department of Pharmaceutics.
Luqmancollege of Pharmacy, Gulbarga.
11.4 / Signature of Co-guide
12. / 12.1 / Remarks of the Chairman & Principal / We will provide all the necessary facilities required for the proposed research work.
So, recommended for registration
12.2 / Signature