Modified Release of Metformin Hydrochloride using Ion Exchange Resin Complex in Floating Mucoadhesive Tablets

Abstract

Background: Metformin hydrochloride (HCl) is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin HCl is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents and very successfully used as drug of first choice. It has 50-60% oral bioavailability.It is believed to be predominantly absorbed in the upper part of the intestine, and estimated time for its complete absorption is approximately 6 h. Clinical trials with metformin have demonstrated decreased bioavailability at higher doses, suggesting saturable intestinal absorption. There is need and scope to increase oral bioavailability of metformin HCl. These details led to an idea of development of SR tablet with more gastric/duodenum retention and was designed as SR tablet using ion exchange principle in floating, mucoadhesive matrix. Aim: The objective of this research was to formulate floating mucoadhesive tablet of metformin HCl in complex with ion exchange resin, for the therapeutic dose of 250 mg. Materials and Medhods: Metformin HCl being cationic drug can be complexed with cation exchange resin like indion 244.This study began with formulation and optimization of drug-resin complex (DRC). Various parameters like the use of batch and column process, complexation time, temperature, and pH were studied and optimized. DRC was characterized by infrared spectroscopy and X-ray diffraction pattern. The efficient drug loading was evident in a batch process using activated indion 244 with a drug-resin ratio of 1:1. Drug complexation enhanced with pH 3.5, temperature 60°C. Infrared spectroscopy revealed complexation of: −NH group of the drug with −C=O stretching of aryl acids of indion 244. Optimized DRC obtained was amorphous in nature. This DRC was put into tablet which could sustain the release of metformin in the favorable region of gastric pH because of inherent slow release from DRC along with a matrix of hydroxylpropylmethylcellulose (HPMC) K100M and Carbopol 974P. HPMC K100M along with sodium bicarbonate made this tablet float and Carbopol 974P gave the additional property of mucoadhesion. The quantity of carbopol optimized first and quantity of HPMC and carbopol using 32 factorial design. Results: The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, floating lag time, floating time, mucoadhesive strength, and in vitro drug release. Tablets thus formulated (Batch M-3) provided sustained release using floating and mucoadhesion approaches over a period of 12 h. The project is open for in vivo studies. Conclusions: Metformin HCl (250 mg) table as drug resin complex in mucoadhesive floating matrix can provide advantage for early cases of diabetics. Floating mucoadhesive tablet having metformin HCl complexed with indion 244 is not available in the market and not yet reported in research paper as per literature survey. This could be one of the attempts to increase the oral bioavailability of metformin HCl.