Formulation Design And Development Of Bentonite Incorporated Trimetazidine Ophthalmic Delivery

Abstract

Trimetazidine (TZ) is a highly soluble and highly permeable BCS-I drug. TZ has a short newlineelimination half life of 3 to 4 h which leads to repeated administration (2-3 times daily). newlineBentonite is reported to be used for extending ocular drug delivery safely in a controlled newlinemanner. Published reports are not available exactly on topically applied ocular delivery newlineof trimetazidine for extended period of time. Bentonite clay based film formulation has newlinebeen prepared for topical delivery of TZ for the control of ocular pressure. TZ newlineophthalmic film formulation has been prepared incorporating bentonite at 1:0.0001 to newline1:0.00005 ratio in hydroxylpropyl methylcellulose (HPMC) matrix by solvent casting newlinemethod. Bentonite combined hydroxypropyl methylcellulose (HPMC)-poloxamer based newlinesol-to-gel formulation has been developed for the prophylactic ocular anti-inflammatory newlineeffect of TZ after corneal application. HPMC-poloxamer sol formulation was prepared newlineincorporating TZ to bentonite at 1:2*10-5 to 1:5*10-6 ratios using cold method, and newlineinvestigations were carried out in carrageenan-induced rabbit eye model. Present study newlinewas undertaken to examine the ocular delivery of TZ in preventing ocular damage and newlinelens opacification. The cytoprotective action of drug has been examined in the newlinecarrageenan-injected ocular damage, and also lipid-peroxidation was carried out newlinemeasuring malondialdehyde (MDA) in rat eye applying trimetazidine film topically. newlineDrug was dissolved in with glucose solution (55 mM) for studying the preventive effect newlineof cataract development. Film formulation showed controlled release of drug and thereby newlineextending the ophthalmic permeation for more than 6 h. Permeation has been extended newlinewith the decrease of bentonite amount in the film. Sustained TZ delivery has been newlinecharacterized by the area under the decreased intraocular pressure (IOP) versus time newlinecurve after topical administered film formulation. In rabbits treated with film newlineformulation TB3, the peak IOP dropped of almost 30% from the baseline at 240 min and newlinepersisted unti