Abstract

DEVELOPMENT, OPTIMIZATION AND ENHANCEMENT OF TRANSCORNEAL PERMEATION OF TIMOLOL MALEATE FROM A NOVEL IN SITU GEL

Umesh D. Laddha*, Chandrakant R. Kokare and Amol A. Tagalpallewar

Abstract

Glaucoma is a chronic disease that causes irreversible blindness. Timolol Maleate is used as first line drug in treatment of glaucoma. Poor ocular bioavailability and therapeutic response shown by accustomed ophthalmic system can be overcome by use of in situ gelling system which undergoes reversible sol to gel phase transition in cul-de-sac by physical stimulation. Present work describes formulation and evaluation of novel pH sensitive in situ gel system of Timolol Maleate. Carbopol 974P was used as pH sensitive polymer with HPMC K15M as viscosity modifier. 32 factorial design was used to study the effect of independent variables viz. concentrations of Carbopol 974P and HPMC K15M on dependent variables like in vitro drug diffusion and viscosity. Optimized batch showed 88.48% drug diffusion upto 8h. Optimized formulation was evaluated for various parameters such as drug release study, isotonicity, texture analysis, preservative efficacy studies, sterility testing as per IP 2010, accelerated stability studies. Ex vivo transcorneal permeability study was carried out on goat eye cornea which showed that EDTA (0.5%) increases drug penetration by 1.90 fold and showed no corneal damage after histological study. In conclusion, prepared formulation is stable, non-irritant and breakthrough in treatment of glaucoma.

Keywords: Glaucoma; in situ gel; transcorneal permeation; polymeric system; optimization and validation.