Formulation design, optimization and in vivo evaluation of a ph and ion responsive ophthalmic in situ gel of forskolin- beta cyclodextrin complex

The poor bioavailability of ocular solution is caused by dilution and drainage from the eye can be overcome by using In situ gel forming ocular drug delivery system prepared from polymers that exhibit sol to gel transition. The objective of the study was to develop optimized formulation of In situ gel of Forskolin (FSK) antiglaucoma agent using pH and Ion activated polymers Carbopol 940 and Sodium alginate respectively as gelling agents, Hydroxy Propyl Methyl Cellulose (HPMC K4M) as viscosity enhancing polymer. The Forskolin (FSK) solid dispersion was prepared by kneeding method in various ratios (1:1 to 1:4) with β- cyclodextrinas solubility enhancing agent. Solid dispersion 1:4 was selected for further formulation of ocular pH and ion activated In situ gels. The 23 factorial design was employed to optimize the formulation considering Carbopol 940, Sodium alginate and Hydroxy Propyl methyl cellulose (HPMC K4M) as independent variables, Sol to gel transition time (sec) and In vitro percentage drug release as dependent variables. Formulations were prepared successfully and assessed for appearance, gelling capacity, pH, drug content, viscosity, in vivo ocular irritation and in vivo intra ocular pressure (IOP) reduction studies and results observed in acceptable range. Based on sol to gel transition time (sec) and in vitro percentage drug release F9 formulation was found to be best optimized formulation from the nine formulations developed by 23 factorial design. The study revealed that the in situ gel system of Forskolin (FSK) sustained the antiglaucoma activity up to 8 h for F9 formulation.