Development and Evaluation of Ophthalmic Drug Delivery System for Glaucoma

Abstract

Brimonidine tartrate (BRT) is a hydrophilic anti-glaucoma medicine available in solution form (Brimopress Eye Drops) in the market. The improved PCL/PLGA and vitamin E TPGS based regulations were studied and evaluated. BRT-PLGA NPs were formulated, and it was observed that the size of NPs was in the range. Surface morphology studies and DSC revealed that BRT-PLGA NPs exhibited a smooth and spherical morphology. From these findings, it can be said that the thermo responsiveness of poloxamer gel is considerably relied on concentration. Higher amount of poloxamer 407 leads to rapid gelation, but at lower gelation temperature. Results showed that gels exhibit greater network and showed rigidity at fixed Poloxamer concentration. In case of BRT-PLGA-NPs loaded carbopol/HPMC based in situ gelling system all formulations were clear and colorless but little translucent due to the opalescent nature of nanodispersion. The highest cumulative release rate of the drug in simulated aqueous humour over 24 h was confirmed in an in vitro evaluation. The developed in situ gel showed a higher ix permeation rate through the goat eye 51.18 ;g.cm-2 .h-1 (PCL NPs) and 50.24 ;g.cm 2 .h-1 (PLGA NPs) in 4 h whereas, marketed eye drop showed 7.618 ;g.cm-2 .h-1 and BRT in situ gel showed 20.56 ;g.cm-2 .h-1 transcorneal flux in 4 h. In addition, novel optimized in situ gel showed sustained action and continuously reduction of IOP till 12 h. The optimized preparation also studied for in vivo ocular irritability and tolerability indicates no signs of discomfort. In vivo ocular irritancy test was performed in the rabbit eye to check the dose related hyperaemia of BRT. Slight redness has been observed in rabbit eyes with not only the marketed eye drop but also finally optimized formulation of BRT (0.1% w/v). Therefore, the reduced concentration of BRT i.e.0.05% and 0.025% was prepared using previously optimized formula. Percent reduction of IOP of 0.05% and 0.025% of BRT NPs based in situ gel showed 34.377;4.21% and 13.61;3.01%