Timolol Maleate In Situ Ophthalmic Mucoadhesive-Thermosensitive Gel: Development and Characterization

Objectives:The purpose of this study was to prepare a sustained delivery mucoadhesivethermosensitive formulation containing poloxamer 338 (P338), poloxamer 188 (P188) and mucoadhesive agents such as chitosan (CHT) and carboxymethylcellulose (CMC) to increase the ophthalmic bioavailability of Timolol Maleate (TM).Materials and Methods: Gels were prepared by mixing different amounts of P338, P188 and mucoadhesive agents in cold isotonic water with a magnetic stirrer.The sol-gel gelation time of the gels was determined using the test tube inversion method.Viscosity measurements and analysis of mechanical properties of gel formulations were carried out.In vitro release using dialysis membrane and ex vivo permeation studies using fresh cow eyes were performed. Results:The gelation times of the formulations containing 20:2.5 (P338:P188) and 0.1% CMC and formulations containing 20:2.5 (P338:P188) and 0.1% CHT were found to be 35 seconds and 26.67 seconds, respectively.Optimally selected CHT mucoadhesivethermosensitive in situ gelling system can successfully control the release of moderately hydrophilic drugs such as TM.In the viscosity study, both formulations showed Newtonian flow, and the viscosity of the CHT gel was found to be higher.CHT gel showed better mechanical properties than CMC gel.The amount of TM penetrating the cow cornea after 24 hours was 73.38%, 71.80%, 67.25% and 60.55% from the CHT gel, CMC gel, TM solution and commercial preparation, respectively. Conclusion:The improved mucoadhesive-thermosensitive in situ gelling system can successfully control the release of TM.The significantly lower drainage of TM into the circulation compared to eye drops provides an advantage in the treatment of glaucoma, and the use of mucoadhesive agents increases drug penetration.