FORMULATION OF DORZOLAMIDE HYDROCHLORIDE IN-SITU PREPARATION FOR TREATMENT OF GLAUCOMA; IN-VITRO, EX-VIVO AND IN-VIVO CHARACTERIZATION

Present study was planned to prepare a dorzolamide hydrochloride in-situ gel by using Carbopol 974 and HPMC K4M to reduce dosing frequency by increasing residence time as well as sustained drug release from the formulation in cul-de-sac. The concentration of both polymers was optimized by using 3² factorial designs with correlating its impact on dependent variables as cumulative in-vitro drug diffusion at the end of 8 h and viscosity at pH 7.4. Polymer composite showed a quadratic model for drug diffusion as well as for viscosity. Comparative in-vitro drug release study by using type II dissolution apparatus confirms sustained drug release characteristics of optimized formulation which showed 89.41% drug release at the end of 8 h as compared to a marketed formulation which showed complete drug release at the end of 3 h. Ex-vivo transcorneal permeability study ensured permeability of drug through the cornea. Histological study on goat eye cornea proved non-irritation potential of the prepared formulation. A comparative in-vivo study between optimized formulation and marketed formulation on normotensive rabbits confirms sol to gel transition of prepared formulation with percent IOP reduction of 32.87 ± 1.54 at the end of 8 h, whereas; marketed formulation failed to control IOP beyond 3 h. Thus, prepared in-situ gel offers more intensive treatment for glaucoma with a reduction in dosing frequency and enhanced patient compliance.