Abstract

An in situ formed non-disintegrating controlled release asymmetric membrane capsular system, offering improved osmotic effect, was used to deliver poorly water soluble drug flurbiprofen (model drug) to demonstrate how controlled release characteristics could be manipulated by design of polymeric capsule with an asymmetric membrane. In situ formed asymmetric membrane capsule was made by dry method via precipitation of asymmetric membrane on the walls of hard gelatin capsule. Effect of different formulation variables were studied based on 23 factorial design, namely, level of osmogen, ethylcellulose and pore former apart from studying the effect of varying osmotic pressure on drug release. Scanning Electron Microscopy showed an outer dense non porous region and an inner lighter porous region for the prepared asymmetric membrane inside and a gelatin layer outside. Statistical test (Dunnett Multiple Comparison Test) was applied for in vitro drug release at P > 0.05. The best formulation closely corresponded to the extra design checkpoint formulation by a similarity (f2) value of 96.88. The drug release was independent of pH but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed Higuchi model and mechanism of release was Fickian diffusion.

Keywords: In-situ, asymmetric membrane capsule, osmotic, factorial design, statistical test, microenvironment