QUALITY BY DESIGN APPROACH IN FORMULATION DEVELOPMENT AND EVALUATION OF IN SITU OPHTHALMIC GEL OF OLOPATADINE HCL

Abstract

Objective: The aim of present study was to apply Quality by Design (QbD) for development of an optimized ion sensitive in situ ophthalmic gel Olopatadine HCl to increase drug residence time, ocular bioavailability and decreased dosing frequency of drug administration. Method: To develop the optimized formulation, 3 2 full factorial design method was adopted. The material attributes and critical quality attributes of the in situ gel were identified. Materials attributes were amount of Sodium Alginate and HPC and CQA's identified were % drug release and viscosity. The formulations were assessed for appearance, gelling ability, sterility, pH, drug content, viscosity, drug release through cellophane membrane, drug release through corneal membrane of goat, and stability study as per ICH guidelines. Formulations F3 and F8 were selected and were again analysed by grid analysis. Result: The optimized batches exhibited all results in acceptable limits. F8 was found to be the best formulation from the nine formulations developed by 3 2 full factorial design. The optimized formulation showed better drug release when compared with marketed formulation. Conclusion: The study revealed that the in situ gelling system of Olopatadine HCl sustained the effect of drug up to 10 hours. The formulation F8 extended the release of drug up to 10 hours as compared to marketed preparation of Olopatadine HCl, Zyopta (solution), which gives 98.39% drug release within 6 hours.