Design and Characterization of pH Responsive Ophthalmic In-situ Gel containing Cromolyn Sodium for Enhanced Drug Delivery

Abstract

Cromolyn sodium, a mast cell stabilizer, is widely used in VKC management but suffers from poor patient compliance due to frequent dosing. In-situ gel systems offer a promising alternative for sustained ocular drug delivery, with polymers like chitosan and HPMC enabling pH-sensitive sol-to-gel transitions upon contact with tear fluid. Five formulations (F1–F5) of Cromolyn sodium in-situ gels were developed using varying concentrations of chitosan and a fixed amount of HPMC K100M. Clarity, pH, gelling capacity, viscosity and drug content were all assessed for the formulations. After sterilizing, the refined formulation (F4) was put through additional testing for sterility, in-vitro drug release, and texture profiling. Formulation F4 (0.35% chitosan) performed well, with the maximum drug concentration (96.2%), clean appearance, quick gelation (30 seconds), good gelling capacity, and the proper pH shift after gelation (4.57 to 6.92). Rheological studies confirmed pseudoplastic behavior, and texture analysis demonstrated suitable gel strength (6.934g), adhesiveness (~ -5g), and spreadability (firmness: 220.274g; work of shear: 172.138g·sec). In-vitro drug release revealed sustained release up to 24 hours (89.91%) compared to 4 hours for marketed drops (98.1%). However, microbial growth in sterility testing highlighted the need for stricter aseptic protocols. The optimized pH-triggered in-situ gel of Cromolyn sodium ensures sustained ocular drug delivery and improved patient compliance, highlighting the promise of chitosan-HPMC systems and the critical need for proper sterilization.