Formulation and Evaluation of Gastroretentive Drug Delivery System for an Anti Diabetic Drug

FORMULATION AND EVALUATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEM FOR AN ANTI DIABETIC DRUG

DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

GANESHA. A

M.PHARM, PART-I,

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDENCE OF

Mr.K.SENTHIL KUMAR, M.Pharm

PROFESSOR

DEPARTMENT OF PHARMACEUTICS

SARADA VILAS COLLEGE OF PHARMACY

KRISHNAMURTHY PURAM, MYSORE. KARNATAKA.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / GANESHA. A
M.PHARM, PART-I
DEPARTMENT OF PHARMACEUTICS
SARADAVILAS COLLEGE OF PHARMACY
KRISHNAMURTHY PURAM, MYSORE.
2. /

NAME OF THE INSTITUTION

/ SARADA VILAS COLLEGE OF PHARMACY
KRISHNAMURTHY PURAM, MYSORE-570004.
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN PHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / 10-09-2010
5. /

TITLE OF TOPIC

/ FORMULATION AND EVALUATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEM FOR AN ANTI DIABETIC DRUG
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 conducted on patients or
other 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-VI
8 / LIST OF REFERENCES / ENCLOSURE-VII
9 / Signature of candidate
10 / Remarks of guide / Recommended
11
12 / Name and designation of
11.1 Guide
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department
11.6 Signature
12.1 Remarks of the
chairman and principal
12.2 Name and designation of principal
12.3 Signature / Mr. K.SENTHIL KUMAR
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
SARADAVILAS COLLEGE OF PHARMACY
KRISHNAMURTHY PURAM, MYSORE. KARNATAKA.
Not applicable
Not applicable
Dr. C. JAYANTHI. M.Pharm. Ph.D
PROFESSOR AND HEAD
DEPARTMENT OF PHARMACEUTICS
SARADA VILAS COLLEGE OF PHARMACY
KRISHNAMURTHY PURAM, MYSORE-. KARNATAKA.
Recommended And Forwarded
Dr.K.J.HANUMANTHACHAR. M.Pharm, Ph.D.
PRINCIPAL
SARADA VILAS COLLEGE OF PHARMACY
KRISHNAMURTHY PURAM, MYSORE-. KARNATAKA
6.0
7.0 / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I
6.1 Need for the study
Oral route has been the commonly adopted and the most convenient route for the drug administration. In the development of oral controlled drug delivery system, one of the main challenges is to modify the GI transit time. Gastric emptying of pharmaceuticals is highly variable and is dependent on the dosage form and the fasted state of the stomach.1 Furthermore, the relatively brief gastric emptying time (GET) in humans which normally averages 2-3hrs through the major absorption zone, i.e., stomach and upper part of the intestine can result in incomplete drug release from the drug delivery system leading to reduced efficacy of the administered dose2. This has led to the development of oral gastroretentive dosage forms.
Gastroretention is essential for drugs that are absorbed from the stomach, drugs that are poorly soluble or degraded by the higher pH of intestine, and drugs with an absorption which can be modified by changes in gastric emptying time. This dosage form improves bioavailability, therapeutic efficacy and may even also allow a possible reduction in the dose because of steady therapeutic levels of drug.3 Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients.4
Diabetes mellitus is a group of syndromes characterized by hyperglycemia, glycosuria, hyperlipedimia, negative nitrogen balance, and sometimes ketonemia. A wide spread pathological changes are, thickening of capillary basement membrane, increase in vessel wall matrix, and cellular proliferation resulting in vascular complications like lumen narrowing, early atherosclerosis, sclerosis of glomerular capillaries, retinopathy, neuropathy, and peripheral vascular insufficiency.
Two major types of diabetes mellitus are
Type I: Insulin dependent diabetes mellitus (IDDM), juvenile onset diabetes.
Type II: Non insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes.
Following classes of oral hypoglycemic agents are used in the treatment of type II diabetes. Sulfonylureas derivatives, first generation include tolbutamide and chlorpropamide, while second generation includes glibenclamide, glipizide, gliclazide, and glimepiride. Biguanides are phenformin and metformin. Meglitinide analogues are repaglinide and nateglinide. Thiazolidinediones derivatives are rosiglitazone and pioglitazone. Glucosidase inhibitors are acarbose and miglitol. These drugs must be administered repeatedly to the diabetic patients.5
ENCLOSURE-II
6.2 Review of literature

Jain SK et al.,6 prepared porous carrier based floating gastro retentive drug delivery system of Repaglinide using calcium silicate as porous carrier, HPMC K4M, ethyl cellulose and carbopol 940 as matrix forming polymers and evaluated for its gastro-retentive and controlled release properties, particle morphology, micromeritic properties, invitro floating behaviour, drug content (%), in vitro drug release, comparison with marketed capsule and in vivo study in albino rat.
Rao MRP et al.,7developed RZM microspheres by solvent diffusion–evaporation. A full factorial design was applied to optimize the formulation. The results of 32 full factorial design revealed that the conc of ethyl cellulose 7 cps (X1) and stirring speed (X2) significantly affected drug entrapment efficiency, percentage release after 8 hrs and particle size of microspheres.
Jaimini M et al.,8 developed Famotidine floating tablets by effervescent technique using two different grades of HPMC K100 and HPMC K15M, these grades of HPMC were evaluated for their gel forming properties. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.
Gambhire NM et al.,9 prepared Diltiazem hydrochloride tablets by direct compression technique, using polymers such as Hydroxy propyl methylcellulose (HPMC, HPMC K100M CR), Compritol 888 ATO, alone or in combination and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer Peppas model, which had a higher value of correlation coefficient (r).
Londhe S et al.,10 developed bi-layer floating tablets for verapamil hydrochloride. Verapamil hydrochloride has pH dependent solubility. Verapamil hydrochloride bi-layer floating tablets have two layers one immediate release layer and second floating sustained release layer. Direct compression method was used to formulate bi-layer floating tablets. All bi-layer formulation float more than 12 hrs and sustained drug release above 12 hrs. Kinetic release study suggests that release mechanism is quasi Fickian.
Yasir M et al.,11 developed once daily SR floatingmatrix tablet for theophylline using psyllium husk as release controlling polymer and compared the release pattern with polymers like HPMC K15 M, sodium bicarbonate, Ac-Di-Sol etc. It was found that Floating duration of the formulation containing psyllium husk alone was less than that containing similar concentration of HPMC K100M. It can be concluded that Psyllium husk can be a promising polymer for gastroretentive floating drug delivery systems in combination with synthetic polymers.
Patel VF et al.,12 developed Ranitidine floating tablets; in which they optimized types of filler, different viscosity grades of HPMC and its concentration. Two fillers namely Avicel pH 102 and Tablettose 80 were used. Study revealed that type of filler had significant effect on release of drug from hydrophilic matrix tablets and floatingproperties.
Hari BNV et al.,13 prepared the floating bead formulations by dispersing nevirapine together with calcium carbonate in a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. The beads containing higher amounts of calcium carbonate demonstrated an instantaneous, complete, and excellent floating ability over a period of 24 hours. The increased amount of the gas forming agent did not affect the time to float, but increased the drug release from the floating beads, while increasing the coating level of the gas-entrapped membrane, increased the time to float, and slightly retarded the drug release.
Gohel MC et al.,14 developed a more relevant in vitro dissolution method to evaluate a Carbamazepine FDDS. The tablet did not stick to the agitating device in the proposed dissolution method. The drug release followed zero order kinetics in the proposed method. The proposed test may show good in vitro in vivo correlation (IVIVC) since an attempt is made to mimic the in vivo conditions.
Li S et al.,15 evaluated the contribution of formulation variables on the floating properties of a gastro floating drug delivery system using a continuous floating monitoring device and statistical experimental design. The formulation was conceived using 2x3 full factorial designs for calcium delivery. HPMC was used as a low-density polymer and citric acid was incorporated for gas generation. Analysis of variance (ANOVA) test on the results from these experimental designs demonstrated that the hydrophobic agent magnesium stearate could significantly improve the floating capacity of the delivery system. High-viscosity polymers had good effect on floating properties.

ENCLOSURE-III
6.3 Objectives of the study

To selecta suitable anti diabetic agent and polymers.
To formulate the gastroretentive systems using suitable polymers.
To evaluate the precompression parameters like compatibility, angle of repose, bulk

density, tapped density, compressibility index.

To evaluate the post compression parameters like thickness, weight variation, drug

content, total buoyancy time.

To carry in-vitro dissolution studies and release mechanism by using different releasekinetic models.

MATERIALS AND METHODS
Materials:
Drug: Any of the antidiabetic drug like Metformin, rosiglitazone maleate etc., will be taken for the study
Polymers: Hydroxy propyl methyl cellulose, xanthan gum, gaur gum etc.
Other excipients: Sodium bicarbonate, tartaric acid, lactose etc.
Reagents: Solvents are of analytical grade.
Instruments: Dissolution apparatus, pH meter, UV spectrophotometer etc.
Methods:Effervescent type/ non-effervescent type/suitable method
ENCLOSURE-IV
7.1. Source Of Data

Library: Sarada Vilas College of Pharmacy
e-library: Sarada Vilas College of Pharmacy

ENCLOSURE-V
7.2. Method Of Collection Of Data
1. Preformulation studies such as

Solubility
Standard calibration
Compatibility of drug with other excipients.

2. Preparation of gastroretentive tablets of antidiabetic drug.
3. Evaluations of gastroretentive tablets

Thickness
Hardness
Weight variation
Friability
Assay
Swelling index
In-vitro drug release studies
In-vitro buoyancy study
Drug release kinetics studies
FTIR

ENCLOSURE-VI
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
No
7.4 Has ethical clearance been obtained from your institute in case of 7.3?
------
ENCLOSURE-VII
LIST OF REFERENCES

Shah SH, Patel JK, Patel NV. Stomach specific floating drug delivery system: a review. Int J PharmTech Res 2009; 1(3):623-33.
Rouge N, Buri P, Doelker E. Drug absorption sites in the gastrointestinal tract and dosage forms for site specific delivery. Int J Pharm 1996; 136:117-39.
Singh BM, Kim KH. Floating drug delivery systems: an approach to controlled drug delivery via gastric retention. J Control Rel 2000; 63:235–59.
Mayavanshi AV, Gajjar SS. Floating drug delivery systems to increase gastric retention of drugs: A Review Research J Pharm Tech 2008; 1(4):165-78.
Tripathi KD. Essentials of medical pharmacology. 5th ed. New Delhi: Jaypee brothers medical publication (p) Ltd; 2003.
Jain SK, Awasthi AM, Jain NK, Agrawal GP. Calcium silicate based microspheres of Repaglinide for gastro retentive floating drug delivery: Preparation and in vitro characterization. Int J Pharm 2005; 107(2):300-9.
Rao MRP, Borate SG, Thanki KC, Ranpise AA, Parikh GN. Development and invitro evaluation of floating Rosiglitazone maleate microspheres. Drug Dev ind pharmacy 2009; 35(7):834-42.
Jaimini M, Rana AC, Tanwar YS. Formulation and evaluation of Famotidine floating tablets. Curr Drug Deliv 2007; 4:51-55.
Gambhire NM, Ambade WK, Kurmi DS, Kadam JV. Development and In Vitro evaluation of an Oral Floating Matrix tablets formulation of Diltiazem Hydrochloride. AAPS Pharm Sci Tech. 2007; 8(3): E166-E74.
Londhe S, Gattani S, Surana S. Development of floating drug delivery system with biphasic release forverapamil hydrochloride: in vitro and in vivo evaluation. J Pharma Sci Tech 2010; 2(11):361-7.
Yasir M, Asif M, Bhattacharya A, Bajpai M. Development and evaluation of gastroretentivedrug delivery system for theopylline usingpsyllium husk. Int J ChemTech Res 2010;2(2):792-9.
Patel VF, Patel NM, Yeole PG. Study of formulation and evaluation of ranitidine floating tablet, Indian J Pharm Sci 2005; 67(6):703-09.
Hari BNV, Brahma RA, Samyuktha RB. Floating drug delivery of nevirapine as a gastroretentive system. J Young Pharmacists 2010; 2:350-5.
Gohel MC, Mehta PR, Dave RK, Bariya NH. A more relevant dissolutionmethod for evaluation of floating drug delivery system. Dissolutiontechnologies 2004; 65(6):22-5.
Li S, Lin S, Daggy BP, Mirchandani HL, Chien TW. Effect of formulation variables on the floating properties of gastric floating drug delivery system. Drug Dev and Ind Pharm 2002; 28:783-93.