FORMULATION AND OPTIMIZATION OF THERMOSENSITIVE IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OCULAR DRUG DELIVERY


Chitra Gupta, Vijay Juyal, Upendra Nagaich

Abstract


Abstract

Objective: Poor bioavailability and short precorneal residence time of ophthalmic formulation are notoriously limiting factor for topical drug administration. Further, the ratio of polymer to drug, plays an integral role in advancement of ocular drug delivery. Present study has focused to identify and optimize the formulation, considering the industrial perspective with variable affecting factors by Box–Behnken design.

Methods: Mixture of solution of Pluronic F-127, Gellan gum and Carbopol were prepared with variable concentration and optimized. Box–Behnken design used in the present study helped to identified the factors affecting the rheology, gelation temperature and MRT. Moreover, optimized formulation was evaluated for ocular irritancy and accelerated stability study.

Results: The ANOVA analysis revealed the significance of various model based on the variable affecting characteristics of polymers ratio. Derived polynomial equation and contour graph help to assume the values of independent variable factors for synthesized novel ophthalmic formulations. Moreover, the accelerated stability study, anti-microbial potential and ocular irritancy reports confirmed the biocompatibility of optimized in-situ drug containing gel with high potency and stability.

Conclusion: Thus, optimized in-situ drug containing gel with multifactorial approaches showed the promising ocular formulation having minimum side effect and high therapeutic efficacy.

Keywords


Ocular in-situ gel; Pluronic F-127; Gellan gum; Carbopol; Box–Behnken design; Bioavailability.

References


Objective: The present study has focused on development and optimization of thermosensitive in-situ ocular drug delivery system for the treatment of conjunctivitis.

Methods: Thermosensitive in-situ hydrogel formulation of moxifloxacin hydrochloride was developed by dispensing variable concentration of pluronic F-127, gellan-gum, and carbopol in distilled water. Viscosity, gelation temperature and mean release time (MRT) were measured by using ‘Brookfield’ viscometer LV-III (spindle no. 40), rheological techniques and dissolution apparatus respectively. Optimization for ideal formulation was carried by ‘Box–Behnken’ design on the basis of prime factors of the formulation including viscosity, gelation temperature, and MRT. Moreover, the optimized formulation was evaluated for accelerated stability study by in vitro drug release, anti-microbial potential by ‘Kirby-Bauer disk diffusion’ method and ocular irritancy assay were done by in vivo analysis.

Results: Optimised thermosensitive in-situ gel, when administered into cul-de-sac region of the eye, it was immediately transformed from sol to gel by multi-dimensional mechanism due to plurionic, gellan-gum, carbopol. The optimized formulation minimizes the chances of formulation failure as well as the concentration on individual polymer which dependence on a single mechanism of gelation. The final optimised formulation consists of plurionic (11.50% w/v), gellan-gum (0.32% w/v), carbopol (0.3% w/v), shows optimum therapeutic effect. Moreover, the accelerated stability study, anti-microbial potential, and ocular irritancy confirmed the biocompatibility of optimized in-situ drug-containing gel with high potency and stability.

Conclusion: Thus, optimized in-situ drug-containing gel with multifactorial approaches showed promising ocular formulation having minimum side effect and high therapeutic efficacy.




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