Composite Ion Responsive In Situ Gel Based on Gellan/Carboxymethyl Cellulose Blend for Improved Gelation and Sustained Acyclovir Ocular Release

Abstract

Quick removal and low therapeutic efficacy are drawbacks of ocular eye drops. In situ gels were developed using gellan gum and/or sodium carboxymethyl cellulose as an ion activated polymer to enhance the residence time of the drug on the ocular surface and improve the efficacy through the sustained release of acyclovir. The solution containing polymer converted to gel through cross-linking reaction with Ca ++ ion present in simulated tear fluid. The optimized formulation (F1 GC: 0.5 % gellan gum+0.5 % carboxymethyl cellulose) showed immediate gelation (within 5 s) that remained for more than 6 h and may prevent drug elimination by tears. The developed formulations were clear and in the pH range of 6.05 to 7.84. The interaction between the carboxyl group of polymers and Ca ++ ions was confirmed by Fourier transform infrared spectroscopy. All the formulations showed satisfactory drug content from 91.13-100.61 %. The gel strength of the formulations increased as the concentration of the polymers increased. The prepared in situ gels exhibited a shear thinning pseudoplastic behaviour that may help in the blinking of the eye. Optimized formulation releases the drug for over 8 h and shows the Fickian diffusion release mechanism. The developed formulation may improve the bioavailability of the drug through longer contact time and controlled drug release in the eye.