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.