“DESIGN AND evaluation ofCONTROLLED GASTRIC floating drug delivery system OF PANTOPRAZOLE”

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY

PATEL PRAGNESHKUMAR MOHANBHAI

M.Pharm, Part-1

DEPARTMAENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Mr. S.MURALIDHAR, M.Pharm,M Phill

ASSOCIATE PROFESSOR

Department of pharmaceutics

Dr. H.L.T College of pharmacy

Kengal, chennapatna -571502

Ramanagara (Dist) Karnataka.

2010-2011

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE, BANGALORE, KARNATAKA

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate and
Address (In Block Letters) / PATEL PRAGNESHKUMAR MOHANBHAI
M. Pharm, Part-I
DEPARTMENT OF PHARMACEUTICS
Dr. H. L. T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA-571502
BANGALORE (RURAL), KARNATAKA.
2. / Name of the Institution / Dr. H. L. T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA-571502
RAMANAGARA (DIST), KARNATAKA
3. / Course of the Study and
Subject / MASTER OF PHARMACY IN PHARMACEUTICS
4. / Date of Admission to the
Course / 10-05-2010
5. / Title of the Topic / “DESIGN and evaluation ofCONTROLLED GASTRIC floating drug delivery system of PANTOPRAZOLE”

6. BREFF RESUME OF THE INTENDED WORK

6.1) NEED FOR THE STUDY

Gastric ulcers1are induced due to many factors like excessive intake of alcohol, chronic smoking, irregular dietary habits, influence of external and internal stress factors, other factors like bacterial infection caused due to helicobacter. Pylori. the current therapy involves administration of antacid preparations, proton pump inhibitors, H2–receptor antagonists& surgery as last option, parallel therapy with antibiotics is recommended if the ulcers are induced due to bacterial infection.

The present study is aimed to design a controlled gastric floating drug delivery system (CFDDS) incorporating proton pump inhibitor drug like Pantoprazole to cure Gastric ulcers, Chronic hyperacidity, Gastric Esophageal Reflux Disease (GERD).Pantoprazole’s labeled indication is for the short-term treatment (no more than 16 weeks) of erosive esophagitis associated with gastroesophageal reflux disease (GERD). It may also show benefit for the maintenance treatment of erosive esophagitis, the treatment of duodenal and gastric ulcers, the prevention of gastro-duodenal damage in patients taking NSAIDs, and as adjunctive therapy with antibiotics for the eradication of Helicobacter pylori.

FDDS is chosen as it has site specific drug delivery, long resident time in stomach is achieved and offers prolonged drug release GFDDS are buoyant tablets which release co2, swell & float in gastric fluid & remain as such for long duration & release the drug in a controlled manner as polymers are used .so, once a day (OD) dose can be designed for effective and prolonged therapy throughout the day and offers patient compliance.

Floating tablets2are novel dosage forms wherein drug delivery is controlled by diffusion through polymers, therefore this work is planned to formulate controlled release floating tablet using drug like Pantoprazole, a Proton Pump Inhibitorand evaluate the tablet for its floating ability, hardness, friability, drug release rate, buoyancy etc. it is also planned to conduct stability studies at different temperature and humidity.

Floating drug delivery system provides better bioavailability for the drugs that are unstable in intestinal or colonic environment3

Based on the mechanism of floatation, delivery system can be classified into two types

  1. effervescent floating drug delivery system
  2. Non- effervescent floating drug delivery system4.

Advantage of floating drug delivery systemare5

Sustained drug delivery system

  1. Site specific drug delivery
  2. Patient compliance

.

6.2) Review of literature

  1. Shoufeng Li, Senshang Lin, Bruce P. Daggy, Haresh L. Mirchandani, Yie W. Chien et al, were described about Effect of Formulation Variables on the Floating Properties of Gastric Floating Drug Delivery System (GFDDS) using a continuous floating monitoring system and statistical experimental design methods, which consisted of an electric balance interfacing with a PC, was designed to perform the continuous monitoring of floating kinetics of GFDDS. Several formulation variables, such as different types of hydroxyl propyl methyl cellulose (HPMC), varying HPMC/Carbopol ratio, and addition of magnesium stearate, were evaluated using Taguchi design, and the effects of these variables were subjected to statistical analysis. The combination of HPMC and Carbopol polymer shows good results.6
  1. V.F.Patel, N.M.Patel and P.G.Yeole,et al, were performed Studies on Formulation and Evaluation of Ranitidine Floating Tablets which highlights the formulation& optimization of Ranitidine Hydrochloride gastric floating tablets. Formulations were optimised for type of filler, different viscosity grades of Hydroxy Propyl Methyl Cellulose (HPMC) & its concentration. Two fillers namely Avicel PH 102 & Tablettose 80 were used.Study revealed that type of filler had significant effect on release of drug from hydrophilic matrix tablets(f 2value41.30) and floating properties.Three different viscosity gradesof HPMC namely K100LV, K4M and K15M were used.It was also observed that Viscosity had a major influence on drug release from hydrophilic matrices as well as on floating properties.7
  1. S.C.Basaket al, were studied formulation and evaluation of an Oral Floating Matrix tablet of Ciprofloxacin and evaluated as Ciprofloxacin being absorbed well in stomach and uppersmall intestine was formulated as floating matrix tablets using gas generating agent (sodium bicarbonate) and hydrophilic polymer Hydroxy propyl methyl cellulose (HPMC). Formulation was optimized on the basis of floating time and in-vitro drug release.Two batches of fabricated tablets containing Ciprofloxacin(580 mg),Sodium bicarbonate(200mg), Hydroxypropylmethylcellulose-K100M(100 mg),lactose 9.7-12% and polyvinyl pyrrolidine 4.8% having hardness between14-14.6%kg/cm2. Showing floating time of about 8 hrs and more.The drug release rate was about 80-89% at the end of 8 hours. Thus showing that gas powered floating matrix tablet is a promising gastric floating delivery system.8
  1. K.Himasankar et alwere formulated gastric floating drug delivery system of Metformin Hydrochloride by using polymers such as HPMC, Xanthan Gum, Guar gum, and Hupu Gum, the gastric floating drug delivery system provided a sustained release effect with good bioavailability for drugs like Metformin having site specific absorption in the stomach of upper part of small intestine.9
  1. kale, R.D.et al, were prepared multiple units floating drug delivery system of piroxicam using an enteric polymer and emulsification solvent evaporation method. the microspheres remained buoyant continuously over the surface of acidic media containing surfactant for the period of 8-12 hours in-vitro. They reported that the in-vitro drug release behavior of the floating microspheres was characterized as an enteric property polymer soluble above ph 7.0, the drug release rates from microspheres changed dramatically above and below ph 7.10
  1. Sharma S,et al,were developed low density multiparticulate system for pulsatile release of Meloxicam they combined the principles of floating and pulsatile drug delivery system. they prepared multiparticulate floating pulsatile drug delivery system using porous calcium silicate and sodium alginate for the time and site specific drug release of Meloxicam.11
  1. EL-Kamal,A.H, et al,were prepared and evaluated Ketoprofen floating oral delivery system the designed sustained release system for Ketoprofen to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microparticles by the emulsion solvent diffusion technique. they used four different ratio of eudragit S100 with eudragit RL to form the floating microparticals. it was found that release rates were generally low in 0.1N Hcl especially in presence of high content of eudragit S.100 while in phosphate buffer PH 6.8, high amounts of eudragit S 100 tended to give a higher release rate.12
  1. Streubel A. et al,were prepared floating microparticles consisting of (1) polypropylene foam powder (2) Verapamil Hcl as model drug and (3) eudragit RS, ethyl cellulose (EC) or polymethyl methacrylate (PMMA) as polymers were prepared with an o/w solvent evaporation method. The effect of various formulation and processing parameters on the internal and external particle morphology, drug loading in-vitro floating behaviour in vitro drug release kinetics, particle size distribution and physical state of the incorporated drug was studied.They reported that the type of significant affected the drug release rate, which increased in the following rank under PMMA<EC< eudragit RS.13
  1. P.G. Yeole. et al, were reviewed about floating drug delivery system: Need and development highlighting factors affecting gastric retention and practical approaches in the development of FDDS.14

6.3) MAIN OBJECTIVES OF THE STUDY

In this present investigation we propose:

  1. To formulate Gastric Floating tablet using excipients like Hydroxy Propyl Methyl Cellulose (HPMC) different grades, Carbopol different grades, Ethyl Cellulose (EC), Na CMC, NaHCO3 Effervescent mixtures, etc for optimum delivery of Pantoprazole.
  2. To evaluate the powder mix for precompression characteristics and tableting Characteristics
  3. To evaluate physical properties like hardness, friability, density etc.
  4. To evaluate its floating properties like floating lag time, floating time, buoyancy.
  5. To evaluate the tablet for precompression characteristics and tabletting characteristic of the powders.
  6. To perform in-vitro dissolution studies.
  7. To evaluate the stability studies

7. MATERIALS AND METHODS:

7.1) 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, Bangalore.
  2. Journal
  3. Analytical chemistry Books
  4. Library
  5. Relevant Books
  6. Internet Source
  7. Scientific abstracts.

7.2 METHODS OF COLLECTION OF DATA

  1. The selected drug will be characterize for various physicochemical properties like organoleptic properties, solubility etc.
  2. an analytical method for estimation of drug will be developed and validated using U.V Spectrophotometer (UV-1700,SHIMAZDU,JAPAN)
  3. Floating tablet containing drug shall be prepared by using various polymers like different grades of HPmC, Carbapol, etc.,
  4. the various powder characteristics like bulk density, angle of repose, carr’s index, compressibility index etc.., will be evaluated.
  5. tablet shall be compressed on ten station rotary tablet compression machine (REMIC INDIA, Ahmedabad ) such tablet shall be evaluated for floating time, weight variation, content uniformity etc.
  6. the effect of polymers and their rations on drug release shall be studied.

7. in-vitro dissolution studies will be carried out using USP Dissolution Apparatus (DISSO

2000,LAB INDIA).

  1. Stability studies will be carried out according to ICH guidelines.
  2. All the data obtained will be subjected for statistical analysis.

7.3 Does the study require any investigation to be conducted on patients/Humans/animals? If so, please briefly

no

7.4 Has ethical clearance been obtained from your institution in case of 7.3

NOT APPLICABLE

  1. LIST OF REFERANCES
  1. AroraS,AliJ,AhujaA,KharRK,BabootaS.Floating Drug Delivery Systems: A Review.AAPS PharmSciTech, 2005;06(03):E372-E390.
  1. Dave BS Amin AF Patel M., Gastro retentive drug delivery system of Ranitidine Hcl formulation and in-vitro evaluation. AAPS pharmaSciTech,2002;5:1-10
  1. Gangadharappa H.V, Pramod kumar T.M and Shiva kumar H.G , Gastric floating drug delivery system .IJPER, 2007; 41 (4): 295-305.
  1. Khatri smriti, Girdhari dheeraj, Pahwa Rakesh, Rachna and Ahmad F.J, RecentAdvances In floating drug delivery system. the Indian pharmacist, 2007; 6 (63):17-24.
  1. Shoufeng Li A1, Senshang Lin A2, Bruce P. Daggy A3, Haresh L. Mirchandani A4, Yie W. Chien A5. Effect of Formulation Variables on the Floating Properties of Gastric Floating Drug Delivery System. Drug Development and Industrial Pharmacy by Taylor & Francis, 2002; 28 (7):783-792.
  1. V.F.Patel, N.M.Patel and P.G.Yeole1, Studies on Formulation and Evaluation of Ranitidine Floating Tablets. Indian.J.Pharm.Sci.,2005; 67(6):703-709.
  1. S.C.Basak,et al,Development and in-vitro evaluation of an Oral Floating Matrix tablet Formulation of Ciprofloxacin, Indian.J.Pharm.Sci, 2004; 66(3):313-316.
  1. K. Himasankar,et al, Design and Biopharmaceutical evaluation of Gastric floating Drug Delivery System of Metformin Hydrochloride. Indian J.Pharm Edu & Research, 2006;40 (1):61-62.
  1. Kale RD , Tayade PT . A multiple unit drug delivery system of Pyroxicam using eudragit polymer, Indian J. Pharma sci, 2007; 69 (1):120-23.
  1. Sharma S, Pawar A. low density multipurticulate system for pulsatile release of Meloxicam Current drug delivery, 2006; 3:87-96.
  1. EL-Kamel AH , Sokar MS, Al Gamal SS, Naggar VF Preparation and evaluation of Ketoprofen floating oral delivery system. Int J pharmaceutics, 2001; 220:13-21.
  1. Streubel A, Siepmann J, Bodmeier R, floating microparticles based on low density foam powder. Int. J. pharma, 2002; 241 (2):279-92.
  1. P.G Yeole, Shaguftha khan and V.F Patel, Floating drug delivery system Need and development, Ind.J. Pharm, 2006;7(3):265-272.
  1. Patel DM, Patel NM, Patel VF, Bhatt DA. Floating Granules of Ranitidine hydrochloride Geliucire 43/01. Formulation optimization using factoral design ,AAPS pharma Sci Tech,2007;8(2):22-24.
  1. K.Muthusamy, Preparation and evaluation of Lansoprazole Floating Pellets, Indian J.Pharm.Sci.,2005; 67(1):75-79.
  1. SinghBN,KimKH.Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention.J Control Release.2000;63:235-259.
  1. TimmermansJ,AndreJM.Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy.J Pharm Sci.1994;83:18-24.
  1. DesaiS,BoltonS.A floating controlled release drug delivery system: in vitro- in vivo evaluation.Pharm Res.1993;10:1321-1325.
  1. YangL,EsharghiJ,FassihiR.A new intra gastric delivery system for the treatment of helicobacter pylori associated gastric ulcers: in vitro evaluation.J Control Release.1999;57:215-222.
  1. ChoiBY,ParkHJ,HwangSJ,ParkJB.Preparation of alginate beads for floating drug delivery: effects of CO2 gas forming agents.Int J Pharm.2002; 239:81-91.
  1. LiS,LinS,DaggyBP,MirchandaniHL,ChienTW.Effect of formulation variables on the floating properties of gastric floating drug delivery system.Drug Dev Ind Pharm.2002; 28:783-793.
  1. LiS,LinS,ChienTW,DaggyBP,MirchandaniHL.Statistical optimization of gastric floating system for oral controlled delivery of calcium.AAPS PharmSciTech.2001; 2:E1.
  1. ThanooBC,SunnyMC,JayakrishnanA.Oral sustained release drug delivery systems using polycarbonate microspheres capable of floating on the gastric fluids.J Pharm Pharmacol. 1993; 45:21-24.
  1. StreubelA,SiepmannJ,BodmeierR.Floating matrix tablets based on low density foam powder: effect of formulation and processing parameters on drug release.Eur J Pharm Sci.2003; 18:37-45.
  1. ErniW,HeldK.The hydrodynamically balanced system: a novel principle of controlled drug release.Eur Neurol, 1987;27:215-220.
  1. ShethPR,TossounianJ.The hydrodynamically balanced systems (HBS): a novel drug delivery system for oral use.Drug Dev Ind Pharm.1984;10:313-339.
  1. HiltonAK,DeasyPB.In-vitro and in-vivo evaluation of an oral sustained release floating dosage form of Amoxycillin trihydrate.Int J Pharm, 1992; 86:79-88.
  1. J.Timmermans and A.J Moes, How well do floating dosage forms float,Int.J.pharm, 1996; 62:207-216.

9. / Signature of the candidate
10. / Remarks of the Guide / Topic selected for Dissertation work is satisfactory.
This can be carried out in our Laboratory.
11. / Name and Designation of
(In Block Letters)
11.1 Guide
11.2 Signature / Mr. S.MURALIDHAR, M.Pharm, M.Phill
ASSOCIATEPROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
Dr. H.L.T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA- 571 502
RAMNAGAR (DIST), KARNATAKA.
11.3 Co-Guide (If any)
11.4 Signature / ------
11.5 Head of the Department
11.6 Signature / Mr.RAVADA RAMESH. M.Pharm
PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
Dr. H.L.T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-571 502
RAMNAGAR (DIST), KARNATAKA.
12 / 12.1 Remarks of the
Chairman and Principal
12.2 Signature / The selected topic is satisfactory. The Dissertation work is feasible in our Laboratory.
Principal, Dr, H.L.T. College of Pharmacy
Kengal, Channapatna.

From

PATEL PRAGNESHKUMAR MOHANBHAI.

M.pharm Part-1

DEPARTMENT OF PHARMACEUTICS

Dr. H.L.T. COLLEGE OF PHARMACY

KENGAL, CHANNAPATNA-571 502

RAMNAGAR (DIST) KARNATAKA.

To

THE REGISTRAR (EVALUATION),

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA BANGALORE

4TH “T” BLOCK, JAYANAGAR,

BANGALORE-560 041.

(THROUGH PROPER CHANNEL)

SUB: SUBMISSION OF SYNOPSIS OF DISSERTATION.

RESPECTED SIR,

HEREWITH, I AM SUBMITTING SYNOPSIS OF DISSERTATION WORK “DESIGN ANDEVALUATION OFCONTROLLED GASTRIC floating drug delivery system OF PANTOPRAZOLE” FOR REGISTRATION IN M.PHARM. (PHARMACEUTICS) OF RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA BANGALORE.

KINDLY ACCEPT THE SAME AND OBLIGE.

THANKING YOU,

YOUR’S FAITHFULLY,

Place : Channapatna. (PATEL PRAGNESHKUMAR MOHANBHAI )

Date :

GUIDE :

Mr. S.MURALIDHAR, M.Pharm,M.Phill

ASSOCIATE PROFEESSOR PRINCIPAL

DEPARTMENT OF PHARMACEUTICS Dr.H.L.T. COLLEGE OF PHARMACY.

Dr. H.L.T. COLLEGE OF PHARMACY. KENGAL, CHANNAPATNA.571502

KENGAL, CHANNAPATNA-571502 RAMNAGARAM(DIST),KARNATAKA

RAMNAGARAM (DIST), KARNATAKA

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