Abstract
Objective: The present research work focuses on experimental design assisted In-situ gel for fixed dose combination.
Significance: Brinzolamide(BZ) BCS class II drug and Timolol Maleate (TM), a BCS class I drug is formulated for obtaining the sustained effect, increased ocular bioavailability and reduction of dose leading to better patient compliance.
Methods: The material attributes were gelrite, hydroxy propyl methyl cellulose K4M(HPMC K4M) and HP-β-CD and critical quality attributes identified were gel strength, mucoadhesive index and percentage of drug release of both drugs. BZ and TM were successfully formulated in ion-triggered In-situ gelling system using Taguchi design with minimum trials.
Results: The final optimized formula 0.5 %w/v gelrite, 0.5 %w/v HPMC K4M, 1:2.5 Ratio of drug to HP-β-CD as well as 150rpm stirring rate exhibited acceptable results with enhanced solubility of BZ. The pharmacodynamic study revealed a decrease in intraocular pressure for In-situ gel (17.3) compared to conventional marketed suspension. Moreover, delayed mean residence time and high AUC (61.237 and 4523.65) of In-situ gel indicates prolonged residence time with sustained release.
Conclusion: In conclusion, excellent ocular tolerance and longer action of gelrite and HPMC K4M. In-situ gel for BZ and TM can be explored as potential alternative to marketed formulation reducing the frequency of administration and improving patient compliance in glaucoma.
Keywords: In-situ gel, HP-β-CD, taguchi design, in-vivo animal study, brinzolamide, Glaucoma.
Graphical Abstract
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