Preparation and formula optimization of cephalexin loaded transferosomal gel by QbD to enhance the transdermal delivery: In vitro, ex vivo and in vivo study

Most antibiotics used in topical formulations are not absorbed by deeper skin layers and subdermal tissues. Hence the skin infections are treated with large doses of oral or parenteral antibiotics which lead to unpleasant side effects with drug resistance. This could be the necessity for the preparation of transdermal drug delivery systems, which addressed the issues with administration. The present study designed to develop cephalexin loaded transferosomal (CPX-TFs) gel for an effective treatment of skin infection by improving transdermal delivery. The transferosomes (TFs) were prepared by thin film hydration method by employing QbD based Box-Behnken design. The major objectives of the study was to prepare CPX-TFs with higher entrapment and lower particle size, to enhance the penetration deeper into the skin layers. The seventeen different batches considering concentrations of phospholipon® 90H, sodium deoxycholate at different temperature condition were prepared and the formula was optimized. These variables showed positive effect on its entrapment efficiency and on particle size of transferosomes. The TFs with lower vesicle size showing better stability whereas in vitro diffusion study demonstrated cumulative release (92.96 ± 2%) up to 24 h. The optimized CPX-TFs were incorporated in carbopol 934 gel (0.25%, 0.5%, 1%, 1.5%, and 2% w/v) by dispersion method. This gel with 96.52 ± 3% (2.5% w/v) drug content demonstrated about 91.26 ± 2% release of CPX over a period of 24 h, showing biphasic drug release pattern (initial burst release in first 6 h then sustaining the release over 24 h). It shows excellent anti-bacterial action against the E coli, S aureus and K pneumonaie. The optimized CPX‒TFs gel presented maximum flux value than pure CPX suspension. The increased in permeation with gradual increased in surfactant concentration was observed. The in vivo pharmacokinetic study shows steady state plasma concentration and Cmax for CPX-TFs gel was found to be 2.3-fold which was comparatively greater than oral CPX suspension. The histopathological study confirms the safety of transdermal application of CPX-TFs gel. It was well tolerated by rat skin. Hence CPX-TFs gel could be the potential delivery system for transdermal administration of CPX for treatment of skin infections. [Display omitted]