Ophthalmic pH Triggered in situ Gelling System of Tobramycin: Formulation and Optimization using Factorial Design

Objectives: The objective of present study was to formulate and optimize ophthalmic pH triggered in situ gelling system of tobramycin in order to enhance residence time and provide prolonged drug release. Methods: Two factor three level full factorial design was applied to study the effect of concentration of carbopol 980 and HPMC K4M on dependent parameters such as viscosity, gel strength and gelling capacity. Overlay plot method was used to optimize the formulation. The optimized formula was evaluated for clarity, pH, viscosity, gel strength, gelling capacity, in vitro drug diffusion, sterility test, ocular irritancy test, Isotonicity test, antimicrobial efficacy and stability studies. Results and Discussion: The results showed that increasing the concentration of carbopol980 and HPMC K4M, there was increased in the gelling capacity, its gelling strength and viscosity. All the formulations had pH around 5. The optimized formulation prolonged the drug release for eight hours which had a composition of 0.48% carbopol980 and 0.52% HPMC K4M. From the kinetic modelling it showed that it followed Higuchi model for drug diffusion. The gel formed in vitro produced sustained drug release up to 8 hr. Results showed no significant change in the results of appearance, pH, viscosity, gelling capacity and drug content when stored at accelerated condition and room temperature for a period of one month. Conclusion: Optimized formulation was sterile, non-irritant, isotonic and stable and also it can be substitute to conventional eye drops formulations of tobramycin which could provide a sustained release for a period of eight hours.