FORMULATION AND EVALUATION OF GASTRORETENTIVE MATRIXTABLETS OF FUROSEMIDE

M. Pharm. Dissertation Protocol Submitted to

Rajiv Gandhi University of Health Sciences, Karnataka

Bangalore – 560041

By

Mr. DEORE KETAN BHASKARRAO B. Pharm

Under the Guidance of

Prof. S.P. THAKKER M. Pharm

Department of Pharmaceutics

SET’s College of Pharmacy, S. R. Nagar,

Dharwad, Karnataka – 580002.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

ANNEXURE-II

PROFORMA OF REGISTRATION OF SUBJECT OF DISSERTATION

1. / NAME OF THECANDIDATE
AND ADDRESS / DEORE KETAN BHASKARRAO
DEPARTMENT OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY,S.R. NAGAR,
DHARWAD-580002.
2. / NAME OF THE INSTITUTION / SET’s COLLEGE OF PHARMACY,
S. R. NAGAR,
DHARWAD-580002
3. / COURSE OF THE STUDY AND SUBJECT / MASTER OF PHARMACY
IN
PHARMACEUTICS
4. / DATE OF ADMISSION TO THE COURSE / JUNE- 2010
5. / TITLE OF THE TOPIC:
FORMULATION AND EVALUATION OF GASTRORETENTIVE MATRIX TABLETSOFFUROSEMIDE
6.
7.
8. /

BRIEF RESUME OF THE STUDY:

6.1NEED FOR THE STUDY:

The oral administration of drug is the predominant and most preferable route for drug delivery.Effective oral drug delivery may depend upon the factors such as gastric emptyingprocess,gastrointestinal transit time of dosage form, drug release from the dosage formand site of absorption of drug. Time controlled oral drug delivery system offer severaladvantages over immediate release dosage forms, including the minimization offluctuation in drug concentrations in the plasma and at the site of action over prolongedperiods of time,resulting in optimized therapeutic concentration and reduced sideeffects, a reduction of the total dose administered (while providing similar therapeuticeffects) and a reduction of the administration frequency leading to improved patientcompliance.1
The gastroretentive drug-delivery system can be retained inthe stomach and assists in improving the oral sustaineddeliveryof drugs that have an absorption window in aparticular region of the GI tract. These systems help in continuouslyreleasing the drug before it reaches the absorptionwindow, thus ensuring optimal bioavailability.The principal of buoyant preparation offers asimple and practical approach to achieve increased gastricresidence time for dosage form and sustaineddrugrelease.2
Furosemide is the loop diuretic. It is a weaker antihypertensive. The bioavailability offurosemide when administered orally is about 60-69%. It is effective for the treatment of edema that may accompany congestive heart failure, cirrhosis of liver. Most important use of furosemide is in the treatment of pulmonary edema associated with congestive heart failure.3
Furosemide has poor absorption in lower intestine & have to increase its absorption in gastric pH i.e. stomach, an attempt is made to formulate furosemide in the form of matrix tablets using various polymers which will be retained in stomach.
6.2REVIEW OF LITERATURE:
Sharma Set.al.,have developedthe floating drug delivery systems of Captopril containing one or more gel forming swellable cellulose polysaccharide. Captopril was used with various grades of HPMC in varying ratios to formulate the floating tablets. Lactose was used as a diluent in the preparation of the tablets. Sodium bicarbonate was incorporated into the tablets to aid buoyancy of the tablets. It was concluded that the formulation containing HPMC K4M-60mg, Sodium bicarbonate-20 mg, lactose-94mg was the best formulation & the extent of drug release was found to be around 85 %. This batch also showed immediate floatation and floatation duration of more than 8hrs.4
Pare Aet.al., have prepared effervescent floating tablets of Amlodipine besylate in ten different formulations by employing different grades of polymers and effervescent agents such as sodium bicarbonate and citric acid. The formulations were evaluated for various physical parameters, buoyancy studies, dissolution parameters and drug release mechanisms. Formulation containing HPMC K4M-125mg, HPMC K15M-40mg, carbopol-40mg, Sodium bicarbonate-60mg, citric acid-30mg,PVP K30-10mgshowed maximum floating time of 24 hrs and gave slow and maximum drug release of Amlodipine besylate spread over 24 hrs and whereas Amlodipine besylate released from marketed tablet was rapid and maximum within 12 hrs.5
Gambhire MNet.al.,have prepared the floating matrix tabletsof Diltiazemby direct compression technique, using polymers such as hydroxypropyl methylcellulose (HPMC, Methocel K100M CR), Compritol 888 ATO, alone or in combination and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of sodium bicarbonate and succinic acid on drug release profile and floating properties were investigated.6
Xu Xiaoqianget.al.,have investigated the development of sustained release tablet of Phenoporlamine hydrochloride because of its short biological half-life. Three floating matrix formulations of Phenoporlamine hydrochloride based on gas forming agent were prepared. Hydroxypropyl Methylcellulose K4M and Carbopol 971P NF were used in formulating the hydrogel drug delivery system. Incorporation of sodiumbicarbonate into matrix resulted in the tablet floating over simulated gastric fluid for more than 6 hrs.7
PatelSSet.al.,have prepared floatingtablets of Clarithromycin containing hydroxypropylmethylcellulose (HPMC), drug and different additives were compressed using wet granulation and D-optimal design technique. The study showed that tablet composition and mechanical strength have great influence on the floating properties and drug release. Incorporation of gas-generating agent together with polymer improved drug release, besides optimal floating (floating lag time <30 s; total floating time >10 h).8
Jaimini Met.al.,have developed floating tablets of Famotidine employing two different grades of methocel K100 and methocel K15M by effervescent technique.These grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, invitro buoyancy and dissolution studies.9
ChandiraMR et.al.,have formulated floating tablets of Itopride hydrochloride as a gastroprokinetic drug. This work was aimed to formulate floating tablets of Itopride hydrochloride using an effervescent approach for gastroretentive drug delivery system to improve the local action and ultimately its bioavailability. The tablets were formulated using hydrophilic polymers HPMC K100M, HPMC K15M and carbopol 934P along with effervescing agent sodium bicarbonate and citric acid. It was found that carbopol has a negative effect on floating behavior but it was used only as the drug release retardant. All the formulations were prepared by direct compression method. Optimizedformulation containing 125 mg HPMC K100M, 40 mg HPMC K15M, and 40 mg carbopol 934P was considered as the best product with respect to in vitro drug release for 24 hours release, total floating time and improved bioavailability and site‐specific action.10
Chander Shekar Bet.al.,have prepared a gastroretentive drug delivery system of Ketoconazole by direct compression technology. HPMC K100LV, HPMC K15M, EthylCellulose and effervescent sodium bicarbonate formed the floating tablet. The prepared tablets exhibited satisfactory physicochemical characteristics. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, invitro buoyancy and dissolution studies.11
Kavitha Ket.al.,have developed a gastroretentive drug delivery system of Rosiglitazone maleate. Floating tablets of Rosiglitazone maleate were developed using gas forming agents, like sodium bicarbonate, tartaric acid and polymers like HPMC K15M and Xanthan gum. The prepared tablets were evaluated in terms of their precompression parameters, physical characteristics, in vitro release, buoyancy and buoyancy lag time.12
6.3OBJECTIVE OF THE STUDY:
  • To carry out compatibility studies between drug & polymers.
  • To develop floating drug delivery system of furosemide.
  • To evaluateformulations for various quality control parameters.
MATERIALS AND METHODS:
7.1SOURCE & COLLECTION OF DATA:
  • Reference books.
  • Indian journal of pharmaceutical sciences.
  • AAPS PharmaSci Tech.
  • International journal of Pharmaceutics, etc.
7.2METHOD OF COLLECTION OF DATA:
  1. MATERIALS:
  • Furosemide
  • HPMC K15M & HPMC K100M
  • Carbopol 934
  • Sodium bicarbonate & Citric acid
  • Other tablet excipients
  1. METHOD OF PREPRATION:
  • Gastroretentive matrix tablet of furosemide:
Chemicals & other reagents required for preparation of gastroretentive matix tablets will be procured from standard company sources.
The drug polymers like HPMC K4M, HPMC K100M along with various excipients will be formulated into tablets bysuitable technique.Different polymers grades & blendsof HPMC & carbopol will be taken for formulation & various parameters as mentioned below will be evaluated.
  1. CHARACTERIZATION OF GASTRORETENTIVE MATRIX TABLET OF FUROSEMIDE:
Following parameters will be evaluated:
Precompression studies
Bulk density
Tapped density
Carr’s index
Angle of repose
Hausner's Ratio
Post compression studies
Thickness
Hardness
Friability
Weight variation
Drug content
Floating lag time
Total floating time
Swelling index
  1. IN VITRO DRUG RELEASE:
Invitro drug release studies of the prepared floating tablets will be carried out for aperiod of 12 hrs using USP XXIII apparatus at 37± 0.5°C and at 50 rpm speed at pH 1.2. at specific time intervals, samples are withdrawn & replaced with same volume of dissolution medium. The samples are then analyzed by using UV spectrophotometer at 274 nm.13
7.3 DOESTHIS STUDY REQUIRE ANY INVESTIGATIONSOR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.
- No.
7.4ETHICAL CLEARANCE :
-Not Applicable.
LIST OF REFERENCES:
  1. Vinod KR, Vasa S, Anbuazaghan S, Banji D, Padmasri A, Sandhya S. Approaches for gastroretentive drug delivery systems.Int J Appl Biol Pharm Technol2010 Aug-Oct;1(2):589-601.
  1. Patel VF, Patel NM. Intragastric floating drug delivery system of Cefuroxime axetil: in vitro evaluation. AAPS Pharm Sci Technol 2006;7(1):E1-E7.
  1. Koechel DA, Diuretics In: Block JH, Beale JM Jr. editors.Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry. 11th ed.Philadelphia: Lippincott Williams & Wilkins 2004. p. 596-621.
  1. Sharma S, Sharma A, Jha KK. The study of Captopril floating matrix tablets using different polymers as release retarding agent. The Pharma Res2009;01:34-40.
  1. Pare A, Yadav SK, Patil UK. Formulation and evaluation of effervescent floating tablet of Amlodipine besylate. Res J Pharm Technol2008Oct-Dec;1(4):526-30.
  1. Gambhire MN, Ambade KW, Kurmi SD, Kadam VJ, Jadhav KR. Development and in vitro evaluation of an oral floating matrix tabletformulation of Diltiazem hydrochloride. AAPS Pharm Sci Techol 2007;8(3):1-9.
  1. Xu X, Sun M, Zhi F, Hu Y.Floating matrix dosage form forPhenoporlamine hydrochloride based on gas forming agent: in vitro and in vivoevaluation in healthy volunteers. Int J Pharm2006;310:139–45.
  1. Patel SS,Ray S,ThakurRS. Formulation and evaluation of floating drug deliverysystem containing Clarithromycin for helicobacter pylori.Acta Pol Pharm-Drug Res2006;63(1):53-61.
  1. Jaimini M, Rana AC, Tanwar YS.Formulation and evaluation of Famotidine floating tablets. Curr Drug Deliv2007;4:51-55.
  2. ChandiraRM, Bhowmik D, Jayakar CB. Formulation and evaluation of gastroretentive drug delivery system of gastroprokinetic drug Itopride hydrochloride. Int JPharm Pharm Sci 2010;2(1):53-65.
  1. Chander Shekar B, Shireesh KR,Nagendra BB. Preparation and evaluation of gastroretentive floating tablets of Ketoconazole.Int J PharmRes Dev2010;2(9):174-84.
  1. Kavitha K, Puneeth KP, Tamizh Mani T. Development and evaluation of Rosiglitazone maleate floating tablets. Int J Appl Pharm2010;2(2):6-10.
  1. Karkhile VG,Karmarkar RR, Sontakke MA, Badgujar SD, Nemade LS. Formulation and evaluation of floating tablets of Furosemide. Int J Pharm Res Dev 2010;1(2):1-9.

9. / SIGNATURE OF THE STUDENT
10. / REMARK OF THE GUIDE
The above mentioned information and literature has been extensively investigated, verified and was found to be correct. The present study will be carried out under my supervision and guidance.
11. / 11.1 NAME AND DESIGNATION
OF THE GUIDE
11.2 SIGNATURE / PROF. S.P. THAKKER M. Pharm.
PROFESSOR AND HEAD,
DEPT. OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
11.3 NAME AND DESIGNATION
OF CO-GUIDE
11.4 SIGNATURE / ------
11.5 HEAD OF THE
DEPARTMENT
11.6 SIGNATURE / PROF. S.P. THAKKER M. Pharm.
PROFESSOR AND HEAD,
DEPT. OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
12. / 12.1 REMARK OF THE
PRINCIPAL
12.2 SIGNATURE / The above mentioned information is correct and I recommendthe same for approval.
Dr. V. H. Kulkarni M. Pharm, Ph.D.,
PROFESSOR & PRINCIPAL,
SET’sCollege of Pharmacy,
S.R.NAGAR, DHARWAD- 580002.

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