The aim of this study was to develop novel microemulsions (MEs) for the transdermal delivery of capsaicin. Microemulsion-based nonionic surfactants consisting of isopropyl myristate as the oil phase, various nonionic surfactants as the surfactant (S), various glycols or alcohol as the co-surfactant (CoS), and reverse osmosis water as the aqueous phase were formulated. Based on the optimal ME obtained from Design Expert, MEs containing a fixed concentration of oil, water or surfactant were prepared while varying the amounts of the other two fractions. The results indicated that the skin permeation flux of low dose capsaicin (0.15% (w/w)) was significantly higher for the selected ME than the commercial product and capsaicin in ethanol (control) by approximately two- and four-fold, respectively. We successfully demonstrated the feasibility of the transdermal delivery of capsaicin-loaded ME using a low concentration of nonionic surfactant and ethanol. Moreover, the optimization using computer program helped to simplify the development of a pharmaceutical product.

Our previous study reported that the Design Expert® Software showed a beneficial role in the development of microemulsions (ME) for transdermal drug delivery. To fully confirm the reproducibility and the reliability of simultaneous optimal ME formulations, the optimal ME formulations predicted by the Design Expert® Software were experimentally formulated and verified for their skin permeability. Ternary phase diagrams were used to predict the optimal ME area, and the ME formulations selected from outside this area were considered as candidate ME systems. Our ME systems were formulated with isopropyl myristate (IPM) as the oil phase, cocamide diethanolamine (DEA) as the surfactant, ethanol as a co-surfactant and water as the aqueous phase. The droplet size, size distribution, electrical conductivity, pH, drug content and skin permeability of the candidate ME systems were monitored. Our findings indicated that the skin permeability of the optimal ME and all of the candidate ME formulations was significantly greater than that of the commercial capsaicin (CAP) product. Our study succeeded in predicting and developing the ME systems for the transdermal delivery of CAP. The simplex lattice design used in this study is experimentally useful for the development of pharmaceutical formulations.