Design And Evaluation Of Compound Metformin Hydrochloride/Glipizide Simutaneously Extended (Controlled) Preparations

The system, which can deliver multi-drugs at the extended rate, is very important to the treatment of various chronic diseases. In this paper, metformin hydrochloride and glipizide were used as the model drugs to prepare compound bilayer sustained release tablets(BT) and compound elmentary osmotic pump controlled release tablets(EOP). Furthermore, the release behaviors of both drugs in vitro and in vivo and the mechanism of two types of extended release tablets were intensively studied.Until now, there were no reports about compound metformin hydrochloride/ glipizide extended release preparations in the research area of pharmacy. In this paper, compound metformin hydrochloride/glipizide bilayer sustained release tablets were developed. The effects of many factors including formulation of drug layers, arts of tablets and the condition of drug release on both drug release behaviors of the bilayer sustained release tablets were investigated. Therefore, three formulations were designed; different physiochemical parameters were used as the evaluation standard and the optimization formulation was obtained. The results indicated that metformin release was fitted with Higuchi equation, while glipizide release followed zero-order equation.In general, both highly and poorly water-soluble drugs were not good candidates for elementary osmotic delivery. However, metformin was a highly soluble drug with the high dose (500mg) while glipizide was a water insoluble drug with the low dose (5mg). So, it was a great challenge to the pharmacists how to provide EOP with satisfactory extended release behaviors of metformin and glipizide. In this paper, sodium carbonate was used to modulate the solubility of glipizide within the core, and metformin was not only one of the active ingredients but also the osmotic agent. The influences of sodium carbonate, membrane thickness and orifice size on the release of both drugs were investigated. The optimal EOP was found to be able to deliver both drugs at a rate of approximately zero order up to 8 hr in pH 6.8, independent of environment media and stirring rate.Moreover, the mechanism of drug release from compound metformin hydrochloride/glipizide elementary osmotic punp tablets was first studied in three aspects: the permeation of membrane, the osmotic pressure of tablet core and the drug delivery...