Statistical Optimization and In Vitro Evaluation of Metformin Hydrochloride Asymmetric Membrane Capsules Prepared by a Novel Semiautomatic Manufacturing Approach

Asymmetric membrane capsules (AMCs) are one of the novel osmotic delivery devices which deliver a wide range of drugs in controlled manner. In the present work, we developed and validated a semiautomatic process by fabricating a hydraulic assisted bench top model for manufacturing AMCs. The capsule walls of AMCs were prepared by dip coating phase inversion process using cellulose acetate butyrate (CAB) as coating polymer and propylene glycol (PG) as plasticizer and pore former. The comparative examination of physical parameters confirmed the consistency, efficiency, and reproducibility of the semiautomatic process over the manual procedure. The SEM studies revealed a thin dense region supported on a thicker porous membrane of the capsule shells. Formulations of AMCs were prepared based on a 23 full factorial design using metformin hydrochloride as the model drug. The effect of formulation variables such as concentration of PG and levels of fructose and potassium chloride were studied on the in vitro drug release using Design-Expert 8.0.2 (USA) software. From the in vitro release studies, it was observed that the concentration of pore former and level of osmogents had a direct effect on the drug release. From the validation studies of the optimized formulation (OPT) with the predicted response, it was observed that the drug release was independent of pH and agitation intensity but dependent on osmotic pressure of the dissolution medium. The OPT followed controlled zero-order release kinetics over a period of 13？h. 1. Introduction Controlled release drug delivery systems have been the research hot spot for the formulation scientists from the last few decades. These delivery systems became popular due to their sustained release and reduction in dosage frequency which leads to the patient compliance. A number of design approaches were available to control or modulate the drug release from a dosage form. The majority of sustained release dosage forms come under the category of matrix, reservoir, or osmotic systems. The application of osmotic pressure for drug delivery was extensively studied and explained by Santus and Baker [1] as the most acceptable approach to achieve the zero-order kinetics. Asymmetric membrane capsules (AMCs) are one of the single core nondisintegrating osmotic controlled systems consisting of drug filled in water insoluble polymer shells [2]. Since the capsule is made of water insoluble semipermeable polymer, the drug release is controlled by osmotic pressure as a major contribution. The in vitro release rate of a drug from an AMC