Process Optimization and Physicochemical Evaluation of Chlorzoxazone -Loaded Nanoemulsion Gel for Enhanced Bioavailability

Chlorzoxazone (CLZ), a centrally acting skeletal muscle relaxant, exhibits inadequate water solubility and reduced bioavailability, limiting its therapeutic effectiveness. In this study, a self-nanoemulsifying drug delivery system (SNEDDS) for CLZ was developed and further transformed into a nanoemulsion-based gel to improve topical delivery. The optimized SNEDDS, prepared using sesame oil, Tween ۸۰, and PEG ۴۰۰, exhibited a particle size of ۲۴ ± ۰.۵ nm, Zeta Potential of –۲۶.۴ mV, and drug release of ۹۸.۰۳% within ۶۰ min, showing excellent agreement with the predicted values. The nanoemulgel was formulated using Carbopol ۹۳۴ and triethanolamine as gelling agents, achieving a drug content of ۹۲.۶۳ ± ۱.۲%. In vitro dissolution studies demonstrated superior drug release compared to that of pure CLZ, with a cumulative release of ۹۲.۰۴% for the optimized formulations. Viscosity (۳۱۲۳ ± ۱۵ cps), spreadability (۱۵.۴ g·cm/s), and pH (۵.۸ ± ۰.۰۲) confirmed the suitability for skin application. Skin permeation studies revealed controlled penetration with significantly higher release profiles than those of conventional formulations. In vivo skin irritation studies in New Zealand white rabbits confirmed that the formulation was a non-irritant, while histopathological analysis showed normal dermal and epidermal architecture, ensuring biocompatibility. Stability studies conducted over ۹۰ days demonstrated that refrigerated samples preserved the drug content (۸۹.۱۶%) and physical properties, whereas room-temperature storage led to phase separation and reduced stability. The CLZ-loaded nanoemulgel successfully combined the solubilization advantages of SNEDDS with the localized delivery benefits of gels, providing a promising strategy for enhanced therapeutic efficacy in the management of muscle spasms.

کلیدواژه ها:

Chlorzoxazone ، muscle relaxant ، histopathology ، SNEDDS ، nanoemulgel ، topical delivery system ، thermodynamic stability