FORMULATION AND EVALUATION OFDOMPERIDONEFLOATING TABLETS

DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

BY

PUNEETH.K.P

M.PHARM, PART -I

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDENCE OF

Dr.K. GOWTHAMARAJAN

PROFESSOR

DEPARTMENT OF PHARMACEUTICS

BHARATHICOLLEGE OF PHARMACY

BHARATHI NAGARA, MANDYA

KARNATAKA-571422

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / PUNEETH.K.P
M.PHARM, PART -I
DEPARTMENT OF PHARMACEUTICS,
BHARTHICOLLEGE OF PHARMACY,
BHARTHI NAGARA,MANDYA,
KARANATAKA-571422

2.

/

NAME OF THE INSTITUTION

/ BHARTHICOLLEGE OF PHARMACY,
BHARTHI NAGARA.

3.

/

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN PHARMACEUTICS
4. / DATE OF ADMISSION OF COURSE / 16-06-2008.

5.

/

TITLE OF TOPIC

/ FORMULATION AND EVALUATIONOF DOMPERIDONEFLOATING TABLETS
6. / BRIEF RESUME OF THE
INTENDED WORK
6.1 Need for the study
6.2 Review of the literature
6.3 Objectives of the study / ENCLOSURE-I
ENCLOSURE-II
ENCLOSURE-III

7.

/

MATERIALS AND METHODS

7.1 Source of data
7.2 Method of collection of data
7.3 Does study require any investigations or interventions to be conducted on patients orother human or animal? If so, please describe briefly
7.4 Has ethical clearance been obtained from your institution in case of 7.3 / ENCLOSURE-IV
ENCLOSURE-V
ENCLOSURE-VI
ENCLOSURE-VII
8. / LIST OF REFERENCES / ENCLOSURE-VIII
9. / SIGNATURE OF CANDIDATE
10 / REMARKS OF GUIDE / Recommended
11. / NAME AND DESIGNATION OF
11.1 Guide
11.2 Signature
11.3 Co Guide (if any)
11.4 Signature
11.3 Head of the department
11.4 Signature / Dr. K. GOWTHAMARAJAN
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
BHARATHICOLLEGE OF PHARMACY
BHARATHI NAGARA, MANDYA
KARNATAKA-571422
Not applicable
Not applicable
Dr.T.SIVAKUMAR
PROFESSOR & HEAD
DEPARTMENT OF PHARMACEUTICS
BHARTHICOLLEGE OF PHARMACY
BHARATHI NAGARA, MANDYAKARNATAKA-571422
12. / 12.1 Remarks of the
chairman and principal
12.2 Signature of the Principal
6.0
7.0
8.0 / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I
6.1 Need for the study
The design of oral controlled drug delivery systems is aimed primarily to achieve more predictable and increased bioavailability.However, this systems have several physiological difficulties, such as inability to restrain and localized oral control drug delivery systems within desired reasons of the gastro intestinal tract and the highly variable nature of the gastric emptying process. Gastric emptying time in humans, which is normally 2-3 hours through the main absorption area(stomach or upper part of intestine),can result in incomplete drug release from oral controlled drug delivery system leading to diminished efficacy of an administered dose. Intimate contact of oral controlled drug delivery system with the absorbing membrane has the potential to maximize drug absorption and also influence the rate of drug absorption .These consideration have lead to the development of oral controlled gastroretentive dosage forms possessing gastric retention capabilities7.
Several approaches are currently used to prolong gastricretention time. These include floating drug delivery systems also known as hydro dynamically balanced systems, swelling systems, expanding systems, high density systems and other delayed gastric emptying devices2. Certain types of drugs can benefit from using gastric retentive part of which include
  1. Drugs acting locally in the stomach.
  2. Drugs that are primarily absorb in the stomach.
  3. Drugs those are poorly soluble at an alkaline pH.
  4. Drugs with a narrow window of absorption.
  5. Drugs that are degrade in colon4
Domperidone is synthetic benzimidazole compound that acts DopamineD2 receptor antagonist. Domperidone is also used prokinetic agent for treatment of upper gastrointestinal motility disorders.After Oral administration, domperidone is rapidly absorbed from the stomach and the upper part of the GIT with fewer side effects. It is weak base with good solubility in acidic pH but significantly reduced solubility in alkaline medium .Such weak base, formulated as an oral controlled release dosage form is exposed to environments of increasing pH with subsequent precipitation of poorly soluble free base
within the formulation that is no longer capable of being released from the formulation. Thusprolonging the gastric retention of domperidone beneficial by improving bioavailability, therapeutic efficacy by possible reduction of dose11.
Hence in the present study an attempt will be made to develop floating tablets of domperidone in order to sustain its release in the stomach and the upper part of the GIT.
ENCLOSURE-II
6.2 Review of literature
  1. Singh S et al., studied the Floating microspheres for oral controlled drug delivery and concluded that floating micro spheres offer various potential advantages for drugs with poor bioavailability because their absorption is restricted to upper GIT and floating micro spheres are retained for longer period of time than single unit dosage form6.
  2. Yeole PG et al., presented a review article about Floating drug delivery systems need and development to achieving a prolonged and predictable drug delivery profile in the gastrointestinal tract to control the gastric residence time, using gastro retentive dosage forms that will provide us with new and important therapeutic option1.
  3. Stops F et al., designed to prolong gastro retention of calcium alginate beads and worked to obtain information regarding the structure,floating ability and changes that occurred when the dosage form was placed in aqueous media15.
  4. Arora S et al., made a review on Floating drug delivery systems with special focus on the principle mechanism of flotation to achieve gastric retention, including the physiological and formulation variables affecting gastric retention, approaches to design single unit and multiple unit floating systems and their classification, summarized the in vitro techniques and in vivo studies to evaluate the performance and application of floating system and concluded that and prolonging gastric retention of dosage form extends the time for drug absorption .Floating drug delivery system promises to be a potential approach for gastric retention 5.
  5. Patel VF, et al., studied on Formulation and evaluation of ranitidine tablets and optimized the formulation for type of filler, different viscosity grades of HPMC and its concentration. The study revealed that type of filler adds significant effect on release of drug from hydrophilic matrix tablet and floating properties. It concluded that the different viscosity grades of HPMC had a major influence on drug release from hydrophilic matrices as well as on floating properties8.
  6. Basak SC et al., studied on Development and in vitro evaluation of an oral floating matrix tablet formulation of Ciprofloxacin, which better absorbed in stomach and upper small intestine was formulated as floating matrix tablet using gas generating agent (sodium bicarbonate)and hydrophilic polymer (hydroxyl propyl methyl cellulose) and concluded that in vitro drug release study of these tablet indicated controlled sustained release for ciprofloxacin and 80-89% release at the end of 8 hrs9.
  7. Muthusami K et al., performed Preparation and evaluation of Lansoprazole floating micro pelletsusing HPMC methyl cellulose and chitosan as a carrier and they concluded that drug loaded micro pellets were found to float on stimulated gastric fluid and simulated intestinal fluid for more than 12 hrs10.
  8. Chavanpatil DM et al.,developeda new gastroretentive sustained drug delivery system with floating, swellable and bioadhesive properties. Various release retarding polymers like psyllium husk, HPMC K100M and swelling agents, cross povidone in combinations are tried and optimized to get release profile for 24hrs3.
  9. Dave SB et al., studiedabout Gastroretentive drug delivery system of ranitidine hydrochloride formulation and in vitro evaluation.The result is of the full factorial design indicated that the addition of stearic acid reduces the drug dissolution due to it’s hydrophobicity and shows sustained release of ranitidine hydrochloride from a gastro retentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride and concluded that addition of gel forming polymer HPMC K4M and gas generating agent sodium bicarbonate was essential to achieve in vitro buoyancy2.
  10. Jaimini M et al., performed the Study on formulation and evaluation of famotidine floating tablets by using different grades of methocel K100 and methocel K 15M by effervescent technique and showing good in vitro buoyancy11
  11. Prajapati TS et al, Develop an optimized gastric floating drug delivery systemcontaining Domperidone as a model drug by using the polymerMixture of HPMCK4M, carbopol, sodium alginate and they investigated combined effect of these polymers on floating behavior and invitro release pattern of drug13.
  12. SahooSKet al., performed the Formulation of floating micro spheres of Ciprofloxacin hydrochloride by Cross linkingtechnique by using thepolymer mixture of sodium alginate and hydroxyl propyl methyl cellulose12.
13. Prabhu et al., studied on Formulation and in vitro evaluation of gastric floating oral tablets of Glipizide. They presented investigation of tablet form of gastric oral floating controlled drug delivery of glipizide by using the retardant,alkalizing and solubilising agent proved to be ideal fashion for extended period of time by maintaining the buonancy.This may over come the solubility problem and clinical problems associated with glipizide in hyperglycemia16.
ENCLOSURE-111
6.3 Objectives of the study
In the present study, the floating drug delivery system (tablets) will be prepared by using Domperidone drug with suitable polymer to achieve sustain release in stomach and upper part of GIT. The work will be scheduled as:
  1. To formulate Domperidone floating tablets using various grades of polymers, effervescent mixture, etc.
  2. To evaluate the powder mix for precompression characteristic and tableting characteristics.
  3. To evaluate physical properties like hardness, friability, density etc.
  4. To evaluate the floating time of the formulation.
  5. To perform in vitro dissolution studies.
MATERIALS AND METHODS
Materials
PolymersHydroxyl propyl methyl cellulose
Carbapol
Ethyl cellulose
Sodium CMC
NaHCO3. etc.,
DrugDomperidone
Other ingredients Lactose, magnesium stearate, Talc, distilled water etc.,
Methods
The following methods can be used for the formulation of Floating drug delivery system.
  1. Gas generating systems.
  2. Hydro dynamically balanced systems.
  3. Low density systems.
  4. Any other suitable method.
ENCLOSURE-IV
7.1. Source of Data
a) Library: BharathiCollege of Pharmacy.
b) e-library: Bharathi College of Pharmacy
ENCLOSURE-V
7.2. Method of Collection of Data
Data on drug will be collected through literature survey and from physiochemical data base such as solubility in various solvents, pH of the drug solution and compatibility of the drug with various polymers.
  1. Preformulation studies
a. Solubility
b. Compatibility.
c.Calibration.
  1. Preparation studies
Preparation of floating tablets by using polymers like hydroxyl propyl methyl cellulose(HPMC) different grades, carbapol different grades, ethyl cellulose(EC),NaCMC,NaHCO3 effervescent mixture etc. foroptimum delivery of floating drug.
  1. Evaluation studies
In vitro buoyancy studies.
In vitro dissolution studies.
Bulk density.
Angle of repose.
ENCLOSURE-VI
7.3. Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
-NOT APPLICABLE-
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
-NOT APPLICABLE-
ENCLOSURE-VII
LIST OF REFERENCES
  1. Yeole PG, Khan S, Patel VF. Floating drug delivery systems: Need and development. Indian J Pharm Sci 2005; 67(3):265-72.
  2. Dave SB, Amin FA, Patel MM. Gastro retentive drug delivery system of Ranitidine hydrochloride: formulation and In vitro evaluation. AAPS Pharm SciTech 2004;5(2):1-6.
  3. Chavanpatil DM, Jain P, Chaudari S, Shear R, Vavia RP. Novel sustained release, swellable and bioadhesive gastro retentive drug delivery system for ofloxacin.Int J Pharm2008 Feb;350(1-2):301-11.
  4. El-kamel AH, Sokar MS, Al Gamal SS, Nagaar VF. Preparation and evaluation of Ketoprofen floating oral delivery system. Int J Pharm2001; 220:13-21.
  5. Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery systems: A review. AAPS Pharm Sci Tech 2005;06(03): 372-90.
  6. Singh S, Singh J, Muthu MS, Mishra B. Floating micro spheres for oral controlled drug delivery. The Indian Pharmacist 2006 Nov: 61-08.
  7. Kumar R, Philip A. Gastro retentive. Dosage Forms for prolonging Gastric Residence time. Int J Pharm Med2007; 21(2):157-71.
  8. Patel VF, Patel NM and Yeole PG. Study of formulation and evaluation of ranitidine floating tablet. IndJ PharmSci 2005; 67(6):703-09.
  9. Basak SC, Nageswara Rao, Manavalan R, Rama Rao P. Development and In vitro evaluation of an oral floating matrix tablet formulation of Ciprofloxacin, Indian J Pharm Sci 2004; 66(3):313-16.
  10. Muthusami K, Govindarazan G, Ravi TK. Preparation and evaluation of Lansoprazole floating micro pellets. Indian J Pharm Sci 2005; 67 (1):75-79.
  11. Jamini M, Rana AC, Tanwar YS. Formulation evaluation of Famotidine Floating tablets.Current Drug Del 2007; 4(1); 51-55.
  12. SahooSK, Mohapatra S, Dhal SK, Behera BC, Barik BB. Formulation of floating micro spheres of Ciprofloxacin hydrochloride by cross linking technique The IndPharmacist April 2007; VI (58):65-68.
  13. Prajapati TS, Patel D, Patel M. Gastric floating tablet matrix tablets: Designand optimization using Combination of polymers.Acta Pharm; 58 (2008);221-29.
  1. Chaudari P,Chaudri S, Nilesh B, Chetan M, Pramod K . Design and Evaluation of Bilayer Floating tablets of Tizanidine HCL. Ind J Pharm Edu Res.2008Feb;42(1):36-47.
  2. Stops F, Fell TJ, Collett JH, Martini GL. Floating dosage forms to prolong gastroretention-The characteristics of calcium alginate beads. Int J Pharm 2008 Feb;350(1-2):301-11.
  3. Prabhu P, Nayari MH, Ahmed MG, Yadav B. Prepartion and Invitro Evalution of Gastric oral Floating Tablets of Glipizide. IndJ Pharm Edu Res2008 Apr-Jun; 42(2):174-183.