Osmotically Regulated Floating Asymmetric Membrane Capsule for Controlled Site-Specific Delivery of Ranitidine Hydrochloride: Optimization by Central Composite Design

Abstract

A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH2.5 (low fed), pH4.5 (intermediate fed), and pH6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl.