Preparation and Evaluation of Metformin Sustained Release Tablet by Using Natural Gum

PREPARATION AND EVALUATION OF METFORMIN SUSTAINED RELEASE TABLET BY USING NATURAL GUM AS RELEASE RETARDANT

DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE

BANGALORE, KARNATAKA.

BY

PARAS PATEL

DEPARTMENT OF PHARMACEUTICS.

UNDER THE GUIDANCE OF

Mrs. THAHERA PARVEEN

ASST. PROFESSOR

MMU COLLEGE OF PHARMACY,

K.K.DODDI, RAMADEVERA BETTA ROAD

RAMANAGARAM-571511

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) / PARAS PATEL
61-GAUTAM NAGAR, MODHERA ROAD, OPP-NIRMA FACTORY, MEHSANA-384002, GUJARAT.
2. /

NAME OF THE INSTITUTION

/ MMU COLLEGE OF PHARMACY,
RAMANAGARAM-571511
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN PHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / 29/06/09
5. /

TITLE OF TOPIC

/ PREPARATION AND EVALUATION OF METFORMIN SUSTAINED RELEASE TABLET BY USING NATURAL GUM AS RELAESE RETARDANT.
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 conduct 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 / FORWARDED FOR APPROAVAL
11.
12. / Name and designation of
11.1 Guide / Mrs. THAHERA PARVEEN
ASST. PROFESSOR
MMU COLLEGE OF PHARMACY,
K.K.DODDI, RAMADEVERA BETTA ROAD
RAMANAGARAM-571511
KARNATAKA
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department / MR.VAZIR ASHFAQ AHMED
ASST.PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
MMU COLLEGE OF PHARMACY,
RAMANAGARAM-571511,
KARNATAKA
11.6 Signature
12.1 Remarks of the
Chairman and principal / SUBMITTED FOR APPROVAL
12.2 Signature
6.
7. / BRIEF REVIEW OF THE INTENDED WORK
ENCLOSURE-I
6.1 NEED FOR THE STUDY
Sustained Release provides the most desirable dosing regimens with effective pharmacokinetic profile and pharmacodynamic response in diabetes treatment. This approach help the patient to lower blood sugar and help body to use insulin more efficiently through maintenance of consistent drug input and it may ease the variability involved in the administration of multiple doses per day. Thus Sustained Release Dosage Form of anti-diabetic drug like metformin tablet improves patient compliance.
Natural polysaccharides play a significant role in the formulation development of a new controlled release dosage forms as well as in human health care system. In recent years, natural polysaccharides are growing rapidly and it continues to remain and important in the new formulation development of the controlled released dosage form.
Natural polysaccharides are much safer than synthetic. They provide many applications in the formulation development of a new controlled release dosage form, such as binder, disintegrator, diluents and release modifier.Therefore, they needs a novel approach to enhance the use of natural polysaccharides in the formulation development of controlled released dosage form, because of the ease availability at an affordable price, high safety margin and higher productivity9.Hence, the present study is aimed to enhance the use of natural plant based polysaccharide as a release modifier to develop metformin sustained released tablets.
ENCLOSURE II
6.2 REVIEW OF LITERATURE

1. Natural Gums and Modified Natural Gums as Sustained-Release Carriers and investigated that natural gums and their derivatives are used widely in pharmaceutical dosage forms, their use as biodegradable polymeric materials to deliver bioactive agents has been hampered by the synthetic materials. These natural polysaccharides do hold advantages over the synthetic polymers, generally because they are nontoxic, less expensive, and freely available. Natural gums can also be modified to have tailor-made materials for drug delivery systems and thus can compete with the synthetic biodegradable excipients available in the market. In this review, recent developments in the area of natural gums and their derivatives as carriers in the sustained release of drugs are explored1.

1. Formulation Variables Affecting Drug Release from Xanthan Gum Matrices at Laboratory Scale and Pilot Scale and explored that diclofenac sodium release from the LS and PS formulations studied was generally linear. Thermal treatment did not appear to have any effect on the rate of drug release; however, hydration of xanthan gum seemed to be affected by the wetness of the powder mass during granulation. Because drug release from xanthan gum matrices proceeds via hydration of the matrix structure, it is important that wetness be properly controlled to avoid variations in rate of drug release among production batches2.

1. Matrix Properties of a New Plant Gum in Controlled Drug Delivery and explored that okra gum controlled the release of paracetamol from a matrix system with as little as 10 percent of the gum in formulation. It compared well with the release from NaCMC matrices. Paracetamol in okra gum matrix tablets showed an anomalous (non-Fickian) release, which approached Case II, time-independent release as the concentration of paracetamol increased to about 20%. The release rate can be further controlled by using a combination of Okra gum and other polymers, and by using suitable diluents like lactose and Avicel. This study suggests that okra gum may be an ideal candidate in the formulation of matrix tablets3.

1. Gum copal and gum damar: Novel matrix forming materials for sustained drug delivery and explored that this study concerns the evaluation of natural gum copal and gum damar as novel sustained release matrix forming materials in tablet formulation. Along with the

physicochemical properties, gum copal and gum damar were characterized for molecular weight, polydispersity index and glass transition temperature and also explored that both gums possess substantial matrix forming property that could be used for sustained drug delivery4.

1. Binding effectiveness of Colocassia esculenta gum in poorly compressible drugs-paracetamol and metronidazole tablet formulations and concluded that the in vitro availability characteristics showed that tablets produced with the new gum show acceptable disintegration time and release profile within a certain range of its concentration in tablets. At 4% w/w nominal concentration of colocassia gum in metronidazole tablets and 6% w/w in paracetamol, tablets show very long disintegration time and prolonged release profile. The binders used for comparison yielded tablets that show better in vitro release characteristics5.

1. Ethephon which increases gumresinosis in Mangifera indica. Ethephon is a nontoxic, environment-friendly, inexpensive and easily available plant growth regulator (PGR) manufactured in India and used extensively in agriculture and horticulture6.

1. Compressed xanthan and karaya gum matrices: hydration, erosion and drug release mechanisms and explored that directly compressed matrices were produced containing either xanthan gum or karaya gum as a release-controlling agent. . These swellable hydrophilic natural gums were used to control the release of varying proportions of two model drugs, caffeine and diclofenac sodium, different solubility in aqueous medium. Xanthan gum displayed a high degree of swelling due to water uptake and a small degree of erosion due to polymer relaxation. Drug release from xanthan and karaya gum matrices depended on agitation speed, solubility and proportion of drug. Both xanthan and karaya gums produced near zero order drug release with the erosion mechanism playing a dominant role, especially in karaya gum matrices7.

1. Evaluating Mucilage from Aloe Barbadensis Miller as a Pharmaceutical Excipient for Sustained-Release Matrix Tablets and explored that natural gums and mucilage have been widely explored as pharmaceutical excipients. Gums and mucilage are biocompatible, cheap, and readily available. The goal of this study was to extract mucilage from the leaves of Aloe barbadensis Miller and to study its functionality as an excipient in pharmaceutical sustained-release tablet formulations. The authors discuss the parameters used to test the mucilage and prepared tablets to see whether they were within

acceptable ranges for pharmaceutical use. Their research shows that mucilage has
potential as an excipient in the formulation of sustained release matrix tablets8.

1. Release behavior of drugs from Tamarind Seed Polysaccharide tablets and explored that tamarind seed polysaccharide can be used for controlled release of both water-soluble and water insoluble types of drugs. Zero order release can be achieved taking sparingly soluble drug like indomethacin from TSP. Using suitable diluents like lactose and microcrystalline cellulose can control the rate of release. For water-soluble drugs the release amount can also be controlled by partially cross-linking the matrix. The extent of release can be varied by controlling degree of cross-linking9.

1. Potential of gum from moringa oleifera to act as a binder and release retardant in tablet formulations: the effect of calcium sulphate dehydrate and lactose diluents on the release of propranolol hydrochloride was studied and resulted that no chemical interaction between gum, drug or mixture of both. Despite of the widely varying physic-chemical characteristics of the excipients, The drug release profile found to be similar. The drug release increased with increasing proportions of the excipient and decreased proportion of gum irrespective of the solubility characteristic of the excipient. In this found that release mechanism is fickian and no evidence that the dissolution or erosion of the excipient has got any effect on the release of the drug .in this relatively small differences in half life values suggest that the nature of excipient used appeared to play a minor role in regulating the release, while the gum content was a major factor10.

ENCLOSURE-III
6.3 OBJECTIVES OF THE STUDY
The main objective of the present investigation is to modify the release characteristic of metformin tablet using a selective plant based natural polysaccharide.
The broad objective is,
To Study the effect of concentration of natural polysaccharide
In vitro drug release behavior from tablets prepared by wet granulation technique
Comparative study of prepared metformin tablets using wet granulation technique with marketed formulation.
MATERIALS AND METHODS
Material
Drug: Metformin
Polymer: Plant based gum.
Additives: Starch, Lactose, Talc, Magnesium Stearate etc.
Equipments: Rotatory Punch Machine, Hot Air Oven, Mortar And Pastel, Sieve etc.
Methods
Development of uncoated metformin tablet using selective plant based natural polymer as a binder by suitable tablet production method.
ENCLOSURE-IV
7.1. Source of Data

1. Library: MMU College of Pharmacy
2. E-library: MMU College of Pharmacy

ENCLOSURE-V
7.2. Method of Collection of Data
Data on drugs will be collected through literature survey and from physiochemical database. Extensive preformulation trials would provide the basis of selection the excipient and system for final formulation development.

1. Prefomulation studies

(a)Physico- chemical evaluation:
(b) Pharmaceutical evaluation:

• Bulk density
• Tapped density
• True density
• Porosity
• Angle of repose
• Haunser ratio
• Carr’s index
• Moisture content

(c) Drug excipient compatibility studies:

• Thin layer chromatographic method
• FTIR analysis and etc.

1. Preparation of tablets:

• Wet granulation method / suitable method
• Evaluation parameters: weight variation, hardness, friability, dissolution etc.

(As per Indian Pharmacopeia).
3. Comparative dissolution studies of marketed formulation.
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 REFERENCE

1. Bhardwaj TR, Kanwar Meenakshi, Lal Roshan, Gupta Anubha. “Natural gum and modified natural gums as sustained-release carriers”. Drug development and industrial pharmacy 2000; 26 (10):1025-1038.

1. Billa nashiru, Yuen Kah-hay. “Formulation variables affecting drug release from xantham gum matrices at laboratory scale and pilot scale”AAPS pharmaSciTech 2000; 1(4) A-30.

1. Kalu VD.Odeniyi MA and jaiyeoba KT. “Matrix properties of a new plant gum in controlled drug delivery” .Archives of pharmaceutical research 2007; 30(7)887-889.

1. Morkhade DM, Fulzele SV, Satturwar PM, Joshi SB. “Gum copal and gum damar: Novel matrix forming materials for sustained drug delivery”. Inter J Pharm Sci 2006; 68 (1-2):53-58.

1. Chukwu KI, udeala OK. “Binding effectiveness of Colocassia esculenta gum in poorly compressible drugs-paracetamol and metronidazole tablet formulations”. Bollettino Chimico Farmaceutico 2000;139(2):89-97.

1. Bhatt JR, shah JJ. “Ethophan enhanced gum resinosis in mango, mangnifra indica linn”. Ind J Experi Bio 1985; 23:330-339.

1. Munday DL, Philip JC. “Compressed xanthan and karaya gum matrices: hydration, erosion and drug release mechanisms”. Inter J Pharm 2000; 203(1-2):179-192.

1. Jani GK, Shah DP, Jain VC, Patel M.J, Vithalani DA. “Evaluating Mucilage from Aloe Barbadensis Miller as a Pharmaceutical Excipient for Sustained-Release Matrix Tablets”.Pharm Tech 2007.

1. Sumathi S, Ray AR. “Release behavior of drugs from Tamarind Seed Polysaccharide tablets” J. Pharm Sci 2002; 5(1):12-18.

1. D. Panda, N.S.K. Choudhury, M. Yedukondalu, S. Si, R. Gupta, “Gum of moringa oleifera as a binger and release retardant”, Ind.J.Pharm.Sci.,2008,70(5):614-618.