Design and development of terbinafine hydrochloride ethosomal gel for enhancement of transdermal delivery: In vitro, in vivo, molecular docking, and stability study

Terbinafine HCl (TH), an allylamine antifungal (BCS-II) drug has poor solubility and high permeability. In the present work, we have investigated the potential of ethosomes as vesicular lipid nanocarrier for enhancement of transdermal application of TH. The ethosomal formulation with varying concentrations of phospholipon 80H (PL80H) and the hydroethanolic solution was optimized and fabricated by applying a 3(2) full factorial design. The impact of independent variables PL80H (X-1) and hydroethanolic solution (X-2) on dependent variables viz., vesicle size (nm), zeta potential (mV), and entrapment efficiency (EE%) were studied. The formulation batch F8 with 100 mg phospholipon 80H (PL80H) and 40% w/v hydmethanolic was considered as most optimized amongst all the batches. The optimized TH ethosomes were embedded into 1% w/v Carbopol 934 gel to study drug release and skin interaction studies. The optimized formulation evidenced with vesicle size 127.39 +/- 2.71 nm, zeta potential - 40.63 +/- 2.77 mV and entrapment efficiency 87.55 +/- 0.47%. The drug release from optimized ethosomal suspension through the cellophane membrane was much better sustained over 24 h compared to the marketed product. Additionally, the zone of inhibition of ethosomal gel against Aspergillus Bravia (fungal strain) was larger than the marketed product. We have also investigated the inhibitory potential of Terbinafine against squalene epoxidase of Aspergillus through molecular docking. The binding interactions have shown favorable results and explained the role of Terbinafine in fungus growth inhibition. The present study demonstrates that ethosomal vesicle has the potential to enhance transdermal delivery without any skin irritation. The TH loaded ethosomes could be one of the prominent approaches for transdermal application in the management of fungal diseases.

Automated summary

The study explored the use of ethosomes as vesicular lipid nanocarriers to enhance transdermal delivery of Terbinafine HCl. The optimized formulation demonstrated improved performance in sustained drug release and antifungal activity, showing potential for effective transdermal application in fungal disease management.