BOX-BEHNKEN DESIGN OPTIMIZATION OF SALICYLIC ACID LOADED LIPOSOMAL GEL FORMULATION FOR TREATMENT OF FOOT CORN

Abstract

Objective: The present research is aimed to design and optimize a liposomal gel formulation of salicylic acid (SA) for enhanced drug permeation, higher skin drug retention, sustained release drug delivery and reduced side effects in the effective treatment of foot corn. Methods: Formulation designing and optimization of SA-loaded liposomes was done by box-Behnken experimental design using the three-factor, three-level approach. Phospholipid content, cholesterol content and drug content were selected as independent variables; while the critical quality attributes (CQAs) of liposomal formulation like particle size, PDI, zeta potential, entrapment efficiency and cumulative % drug release were considered as response variables. The SA-loaded liposomes were prepared by ethanol injection method and were characterized for desired CQAs. Finally, topical gel formulation of SA-loaded liposomes was developed and evaluated for drug content, homogeneity, spreadability, in vitro drug release, drug release kinetics, ex-vivo drug permeation and skin retention properties. Results: The particle size, PDI, zeta potential, entrapment efficiency and cumulative % drug release of SA-loaded liposomes was found to be 261.2 nm, 0.28, 0.7 mV, 57.53% and 99.57%, respectively. Developed topical gel formulation of SA-loaded liposomes exhibited a sustained drug release profile (64.48% cumulative release over 360 min) following Higuchi model kinetics. The developed formulation showed almost 2-fold enhanced drug permeation (i.e., 26.50%) and more than 2-fold higher drug retention (i.e., 10.90%) on porcine ear skin as compared to the plain salicylic acid gel. Conclusion: The SA-loaded liposomes and developed topical gel formulation possessed all desired CQAs. The in vitro drug release kinetics, ex-vivo drug permeation and skin retention studies confirmed the suitability of the developed formulation for topical application in the effective treatment of foot corn.