FORMULATION, IN-VITRO RELEASE KINETICS AND STABILITY INTERPRETATION OF SUSTAINED RELEASE TABLETS OF METFORMIN HYDROCHLORIDE Original Article SUDIPTA DAS*, ARNAB SAMANTA, HIMADRI SEKHAR DE PG Research Laboratory, Department of Pharmaceutics, Netaji Subhas Chandra Bose Institute of Pharmacy, Chakdaha, Nadia 741222, West Bengal, India. Email: sudipta_pharmacy@rediffmail.com Received: 29 Dec 2014 Revised and Accepted: 22 Jan 2015 ABSTRACT Objective: The objective of the present study was to formulate, study the in-vitro release kinetics and stability of sustained release tablets of metformin hydrochloride. Methods: Sustained release formulations that would maintain the plasma level for 8 – 12 h might be sufficient for daily dosing of metformin. The granules of metformin hydrochloride were prepared by wet granulation method using polymers such as ethyl cellulose (EC) and hydroxyl propyl methyl cellulose E15 (HPMC E15). Results: The granules were evaluated by determining the angle of repose (26.01 0 ±0.11 0 to 31.95 0 ±0.10 0 ), bulk density, tapped density, Hausner ratio and Carr’s index. It shows satisfactory results. The tablets were subjected to measurement of thickness (4.78 ± 0.07 to 5.20±0.13 mm), weight variation (within limit), drug content (98.08±0.20 to 99.22±0.22%), hardness (9.27±0.16 to10.30±0.97 kg/cm 2 ), friability (0.2to 0.3%w/w), and in- vitro release studies. Conclusion: It was found that as the concentration of HPMC increased the drug release rate declined due to formation of viscous layer. The release can be fine tuned by adding a hydrophobic polymer like EC in the hydrophilic matrix of HPMC. The release mechanisms were analyzed and were found that the release data was best fitted with Higuchi equation although there is no significant difference between the correlation coefficients of Zero-order and Higuchi model. The result also shows different parameters of stability studies and compare with initial results of different batches. Keywords: Metformin Hydrochloride, Sustained release, HPMC E15, EC, Release kinetics, Stability. INTRODUCTION Now-a-days conventional dosage forms of drugs are rapidly being replaced by the novel drug delivery systems. Among, these the sustained release dosage forms have become extremely popular in modern therapeutics. Sustained release dosage forms are designed to release a drug at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects. The main advantages of sustained release tablets are uniform release of drug substance over time and reduction of frequency of intake [1]. Metformin hydrochloride is an orally administered biguanide derivative, which is widely used in the management of type – II diabetes mellitus, in particularly in overweight and obese people and those with normal kidney function. Limited evidences suggest metformin may prevent the cardiovascular and possibly the cancer complications of diabetes. Metformin has an oral bioavailability of 50–60% under fasting condition, and is absorbed slowly. Peak plasma concentration (Cmax) is reached within one to three hours of taking immediate-release metformin and four to eight hours with extended-release formulations [2]. The plasma protein binding of metformin is negligible, as reflected by its very high apparent volume of distribution (300–1000 lit after a single dose). Steady state is usually reached in one or two days [3]. Many researchers investigated or formulated metformin hydrochloride tablets using various natural, semi- synthetic and synthetic polymeric materials. Hence, in the present work, our attempt was to formulate metformin hydrochloride sustained release tablets using combination of two polymers such as hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC) or their mixture to evaluate in-vitro release characteristics and to predict the release pattern with kinetic equations. MATERIALS AND METHODS Materials Metformin HCl was obtained as gift samples from Drakt Pharmaceutical Pvt Ltd., Baroda, Gujrat. Ethyl cellulose (EC), hydroxy propyl methyl cellulose E15 LV Premium (HPMC-E15), talc and magnesium stearate were purchased from Loba Chemie Pvt. Ltd (Mumbai). Starch was procured from Nice Chemicals (Cochin). Microcrystalline cellulose, di-sodium hydrogen phosphate and potassium di-hydrogen phosphate were purchased from Merck Specialties Pvt. Ltd., Mumbai, All those chemicals or reagents were used as supplied without any further purification. Study of physical interaction between drug and polymer [4] Differential Scanning Calorimetric (DSC) was carried out by scanning the samples of pure drug (Metformin HCl), mixtures of two polymers (HPMC and EC), and the formulation, using DSC (Pyris Diamond TG/DTA, PerkinElmer, SINGAPORE) at nitrogen atmosphere (150 ml/min). Platinum crucible was used with alpha alumina powder as reference. Preparation of granules [5] The tablets, each containing 500 mg of Metformin HCl, were prepared by wet granulation technique. The composition of various formulations of the tablets with their codes is listed in table 1. The composition with respect to polymer combination was selected on the basis of trial and error method of tablets. A batch of 20 tablets was prepared with each formula. The drug (Metformin HCl), polymers (HPMC and EC) and other excipients were mixed. The granulation was done manually with a starch solution (5%). The wet mass was passed through a 22 mesh sieves and the wet granules produced were first air dried for 30 minutes and finally at 45-50 0 C in for 60 minutes. The dried granules were sized by a sieve. Then magnesium stearate and talc were added as a lubricant and glidant respectively. Compression was carried out using single punch tablet compression machine (B. D. Instrumentation, Gujarat) at a constant compression force. All the tablets were stored in airtight containers for further study. Prior to compression, granules were evaluated for their flow and compressibility characteristic. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 3, 2015 Innovare Academic Sciences