Optimization and in vivo evaluation of triamcinolone acetonide loaded in situ gel prepared using reacted tamarind seed xyloglucan and kappa-carrageenan for ocular delivery.

In the current work, triamcinolone acetonide (TAA) loaded dual responsive in situ gelling system was designed and optimized using reacted tamarind seed xyloglucan (RXG) (thermoresponsive) and kappa-Carrageenan (κ-CRG) (ion-sensitive) polymers. Tamarind seed xyloglucan (TSX) was subjected to purification followed by enzymatic treatment to produce RXG with ~40 % reduction in galactose content compared to TSX. RXG was characterized using size exclusion chromatography, Fourier transform infrared and proton nuclear magnetic resonance spectroscopy to confirm the ~40 % reduction in galactoside content compared to TSX. The proportions of RXG and κ-CRG in the in situ gels (TAA loaded RXG-κ-CRG) were optimized based on their rheological properties. The optimized in situ gel exhibited good flow properties at 25 °C, but transformed rapidly into a stronger gel in the presence of STF at 35 °C. The optimized formulation had strong mucoadhesion with good spreadability on the surface of excised goat cornea. The drug release followed zero-order kinetics from the optimized in situ gel. Ex vivo ocular toxicity studies indicate that the optimized formulation was well tolerated. The ocular pharmacokinetic studies in rabbits showed significantly higher and sustained vitreous humor exposure of TAA for optimized in situ gel compared to hydroxypropyl-β-cyclodextrin based aqueous suspension of TAA.