D-optimal Design and Development of Microemulsion Based Transungual Drug Delivery Formulation of Ciclopirox Olamine for Treatment of Onychomycosis

The objective of the present study was to design and develop a microemulsion based transungual drug delivery formulation of ciclopirox olamine using colloidal carrier for treatment of onychomycosis. Capmul PG8 was selected as oil phase due to the high solubility of ciclopirox in it as compared to other oils and Cremophor EL and Transcutol P were used as surfactant and cosurfactant respectively. Pseudoternary phase diagrams were constructed using different ratio of S-mix (surfactant: cosurfactant). The phase diagram obtained from 1: 3 ratio showed largest microemulsion region. The construction of microemulsion was further optimized by D-optimal mixture design, taking oil, S-mix and water as independent variables and globule size, transungual flux, and nail drug loading as response variables. Mathematical equations and response surface plots were used to correlate the dependent and independent variables. The optimized composition of microemulsion was predicted by numerical optimization technique on the basis of the highest desirability value. The predicted optimized microemulsion which contained 2% oil, 40% S-mix, and 58% water was incorporated into Carbopol 940 gel base and evaluated for transungual drug permeation. The optimized microemulsion based gel formulation showed globule size (25.8 +/- 1.2 nm), transungual flux (0.436 +/- 0.014 mu g/cm(2)/h), and drug loading in nail plate (82.89 +/- 5.74 mu g) which was in close agreement with the predicted value of response variable by the optimization software, i.e. 26.145 mm, 0.431 mu g/cm2/h, and 81.023 mu g, respectively. These results confirmed that the D-optimal mixture design can be successfully employed for designing and development of microemulsion based formulation of ciclopirox olamine.