Formulation and optimisation of Ozenoxacin topical nano-emulgel including a comprehensive methodology to qualify and validate the critical parameters of an in-vitro release test method and ex-vivo permeation test

Abstract

Objective The purpose of this study was to formulate, optimize Ozenoxacin topical nano-emulsion using factorial design followed by to prepare and evaluate nano-emulgel using validated in-vitro release testing (IVRT) technique for determination of Ozenoxacin release rate along with ex-vivo permeation testing (EVPT). Significance: Nano-emulgel is a proven delivery system for poorly soluble substances works by enhancing the solubility and bioavailability. Factorial design provides a systematic and efficient means to study the effect of multiple factors on responses. IVRT is an USP compendia technique utilized for performance analysis of semi-solid formulations. Methods Nano-emulsion formulation optimization was done with factorial design, evaluated for globule size and % entrapment efficiency (EE). Nano-emulgels were characterized for assay, organic impurities, rheological behavior, IVRT, EVPT, and skin retention studies. IVRT validation was executed using vertical diffusion cells (VDCs). Results Ozenoxacin nano-emulsion was optimized with 1:1 ratio of Oil: Smix, 3:1 ratio of Surfactant:Co-Surfactant, and 15000 RPM of homogenization speed which resulted 414.6 ± 5.2 nm globule size and 92.8 ± 2.1% entrapment efficiency. Results confirmed that IVRT and Reversed Phase – High Performance Liquid Chromatographic techniques were validated as per regulatory guidelines. In-vitro, ex-vivo drug release, and skin retention from the optimized nano-emulgel formulation was comparatively higher (∼1.5 times) than that from the innovator (OZANEXTM) formulation. Conclusions Based on these results, Ozenoxacin nano-emulgel can be considered an effective alternative and was found to be stable at 40 °C/75% RH and 30 °C/75% RH storage condition for 6 months.