Statistical Optimization of Miconazole Nitrate Microemulgel by using 23 Full Factorial Design

Abstract

Miconazole nitrate is a broad-spectrum antifungal agent, poorly water-soluble drug, and is used to treat superficial fungal infections. Microemulgel could increase drug deposition over to the skin. Therefore, the aim of this study was to prepare 2% miconazole nitrate transparent micro emulgel that contains 99% w/w liquid. Preliminary screening of oils and polymers was carried out. Oil phase of the microemulgel selected based on maximum solubility of miconazole nitrate in oil. A 23 full factorial design was used to check the effect of cinnamon oil (X1), HPMC K4M (X2) and tween 20 (X3) on viscosity (Y1) and % of cumulative drug release at 6 hours (Y2). Multiple linear regression analysis, ANOVA and graphical representation of the influence factor by 3D response surface plots were performed using Design Expert 7.1.5. A checkpoint batch was prepared to validate the evolved model. Optimized batch F5 was found to be stable and it showed globule size 26 ± 3 µm. In Ex-vivo drug permeation study batch, F5 was shown 87.05 ± 2.42% drug released after 6 hours and drug deposition on the upper layer of skin was found 52.5%. Accelerated stability study showed no significant change in the micro emulgel parameters within three months, and similarity factor f2 was 91.05 ± 1.67 %. Therefore, 2% miconazole nitrate micro emulgel was providing an effective treatment against topical infections.