Systematic Development And Evaluation Of Proniosomal Gel Derived Niosomes For Ocular Delivery Of Selected Anti Glaucoma Drugs

Abstract

The aim of the present study was to prepare and evaluate sustained release proniosomal gel formulation of Timolol maleate and Forskolin, as a potential formulation for the treatment of glaucoma. Various batches of Timolol maleate and Forskolin proniosome gel was prepared by coacervation phase separation technique using varying concentration of cholesterol and non-ionic surfactants. Proniosomes were evaluated for particle size, surface charge, entrapment efficiency and drug release studies. Visual inspection showed that proniosomal dispersions were white creamy gel in appearance and showed no sign of phase separation. Particle size of prepared proniosome was suitable for ocular application. The decrease in the surfactant: cholesterol ratio from 1:3 to 1:1 resulted in an increase in the size of the vesicles. The zeta potential value was found in the range of -23.5 to -34.7 mV and -23.4 to -34.1 mV for Timolol maleate Proniosome and Forskolin Proniosome respectively. For Timolol maleate proniosome, the entrapment efficiency ranged from 78.3±0.3% to 97.7±0.8%. Entrapment efficiency of Forskolin loaded proniosome was found in the range of 84.38% to 98.51%. Formulation P3 prepared using span 20 and cholesterol in 3:1 showed the highest entrapment efficiency (98.51%). IOP lowering activity of the Timolol maleate and Forskolin proniosome was better as compared with marketed eye drops (Timolet). Ocular pharmacokinetics studies revealed that the relative bioavailability of Timolol maleate proniosomal gel T10 showed higher AUC (2858±89.56 ng h/ml) (p lt0.001), when compared with commercial eye drops (AUC; 1240±56.91 ng h/ml). Forskolin proniosomal gel P3 showed higher AUC (2858±89.56 ng h/ml), when compared with plain eye drops (AUC; 1240±56.91 ng h/ml). Thus, it can be concluded from the available data that intraocular permeation of Forskolin was significantly improved by formulating it as proniosomal gel.