Temperature-dependent phase transition microemulsions for enhanced transdermal delivery of finasteride and silodosin

Finasteride and silodosin are potential combinations for management of benign prostatic hyperplasia (BPH). Simultaneous transdermal delivery can overcome reasons of their poor oral bioavailability. This was achieved via menthol-based microemulsion (ME) which can undergo thermoresponsive phase transition. Pseudoternary phase diagrams were constructed at room temperature and 32 °C using menthol (oily phase) and Tween 80 (surfactant) in absence and presence of ethanol or propylene glycol as cosurfactants. In absence of cosurfactant, phase behavior depended on temperature with part of liquid crystal (LC) zone changing to microemulsion at 32 °C. Cosurfactant abolished LC/gel zones irrespective to temperature. Microemulsion formulations were selected from the area undergoing LC/ME thermoresponsive transition. These were evaluated for viscosity, droplet size, drug release and skin permeation. Characterization confirmed nanosized droplet and viscosity measurement confirmed thermoresponsive behavior in absence of cosurfactant. MEs showed lower release compared to saturated aqueous solutions. MEs resulted in significant increase in transdermal flux of finasteride and silodosin compared to aqueous control with ethanol containing system producing the highest flux. Simultaneous loading of finasteride and silodosin in microemulsions modulated thermodynamic activity. However, their flux remained significantly higher than aqueous suspension. Thus, the study introduced thermoresponsive microemulsion as efficient system for simultaneous delivery of finasteride and silodosin.