Formulation, Optimization and Characterization of Fluconazole Loaded Ethosomal and Liposomal Vesicular Systems for Transdermal Drug Delivery

Abstract

Transdermal drug delivery systems (TDDS) have emerged as an effective alternative to conventional drug administration routes by overcoming limitations such as first-pass metabolism, fluctuating plasma drug concentration, and poor patient compliance. However, the barrier property of the stratum corneum restricts the permeation of many therapeutic agents through the skin. Vesicular carriers such as ethosomes and liposomes have demonstrated significant potential in enhancing transdermal permeation and improving therapeutic efficacy. The present study was aimed at the formulation, optimization, and characterization of fluconazole-loaded ethosomal and liposomal vesicular systems for enhanced transdermal delivery. Ethosomes were prepared by a modified hot method, while liposomes were prepared using the thin film hydration technique. Optimization of the formulations was carried out using a Taguchi Design of Experiments (DoE) approach. Vesicle size and entrapment efficiency were selected as the major response variables for optimization. The prepared ethosomal formulations exhibited vesicle sizes ranging from 161.08 ± 3.214 nm to 552.82 ± 1.254 nm with entrapment efficiency ranging from 64.08 ± 1.213% to 90.83 ± 1.241%. Among all batches, formulation TE4 showed the smallest vesicle size of 161.08 ± 3.214 nm, whereas formulation TE2 exhibited maximum entrapment efficiency of 90.83 ± 1.241%. The optimized ethosomal formulation EF2 showed vesicle size of 368.4 nm and entrapment efficiency of 85.50%. Similarly, liposomal formulations demonstrated vesicle sizes ranging from 126.79 ± 1.175 nm to 510.13 ± 1.154 nm and entrapment efficiency ranging from 55.12 ± 1.241% to 91.70 ± 1.029%. Formulation TL4 exhibited the minimum vesicle size of 126.79 ± 1.175 nm, while formulation TL6 showed maximum entrapment efficiency of 91.70 ± 1.029%. Response surface analysis confirmed that phospholipid concentration and ethanol content significantly influenced vesicle size and drug entrapment. The study demonstrated that optimized ethosomal and liposomal vesicular systems possess suitable physicochemical characteristics for effective transdermal delivery of fluconazole and may serve as promising carriers for enhanced antifungal therapy.