Formulation, characterization, optimization and in-vivo evaluation of methazolamide liposomal in-situ gel for treating glaucoma

Abstract

The rationale of this study was to formulate topically effective sustained release ophthalmic Methazolamide (MTA) liposomal in-situ gel. Lipid film hydration method was employed for the preparation of MTA liposomes consisting of lecithin and cholesterol. Optimization of the MTA liposomes by Design-Expert software was done to evaluate the effect of cholesterol and drug in varying concentrations using a 32 factorial design. Encapsulation efficiency and particle size were considered as dependent variables. Drug encapsulation was increased by increasing cholesterol as well as drug concentration. The optimized batch showed encapsulation efficiency of 74.12 ± 0.52% and particle size was found 193.2 ± 1.34 nm. The liposomal gel was prepared by incorporating MTA liposomes in Carbopol 934 gel.The final formulation showed a pH of 7.1 ± 0.05, spreadability of 0.8 ± 0.1. In vitro release studies of MTA liposomes and MTA liposomal gel were compared. In comparison to MTA solution, MTA liposomal gel showed a significant reduction (p < 0.05) in intraocular pressure (IOP). Area under % decrease in IOP Vs time (hr) curve (AUC0–8hr) was found to be 58 ± 0.03, 174 ± 0.04, and 222 ± 0.03 hr−1 for MTA drug, MTA liposomes, and MTA liposomal gel respectively. MTA Liposomal gel, as opposed to traditional eye drops, may be a suitable delivery medium for ocular distribution, with the benefits of more intensive glaucoma treatment, lower dosage, and increased patient compliance.