DESIGN AND OPTIMIZATION OF CONTROLLED RELEASE OCULAR INSERTS OF DORZOLAMIDE HYDROCHLORIDE AND TIMOLOL MALEATE FOR TREATMENT OF GLAUCOMA

摘要

Goal of the present investigation was to formulate ocular inserts of dorzolamide hydrochloride and timolol maleate for the treatment of glaucoma. Ocular inserts of dorzolamide hydrochloride and timolol maleate were prepared using different polymers ethylcellulose, Eudragit RL 100, and Eudragit RS100 by solvent casting method with an objective to increasing the contact time, achieving controlled release, reducing in frequency of administration, and improving therapeutic efficacy. The drug-excipients interaction was studied by Fourier transform infrared spectroscopy (FTIR) studies. Prepared ocular inserts were evaluated for their physicochemical properties such as uniformity of thickness, weight uniformity, tensile strength, percentage elongation, drug content, moisture loss, moisture absorption. The in vitro diffusion of drug from the inserts was studied using the classical biochemical donor – receptor compartment model fabricated in the laboratory and the formulation that showed better release profile was subjected to in vivo studies on albino-rabbits. Ocular irritation study was performed using healthy albino rabbits and confirmed that there was no irritation in the rabbit eyes. All the inserts were found to be uniform thickness and uniform weight. The inserts possessed good tensile strength and percentage elongation. All the formulations followed a first order release pattern. Optimized formulation RSRL3 showed high correlation coefficient (R = 0.996 & 0.995 respectively for dorzolamide HCl & timolol maleate) between in vitro and in vivo release. Stability study was carried out on RSRL3 formulation and showed no significant changes in the drug content as well as physical characteristics of the film.