QbD Approach in the Formulation and Evaluation of Miconazole Nitrate Loaded Ethosomal Cream-o-gel

Abstract

The present study aims to prepare Miconazole Nitrate loaded Ethosomes using QbD principle and formulating them as a suitable dermatological cream-o-gel for enhanced antifungal activity, skin permeation and bioavailability in the treatment of Candidiasis. Central composite 32 factorial design was used for investigating the effects of two variables, concentration of soya lecithin (X1) and ethanol (X2) on the responses of particle size and % entrapment efficiency (% EE) which were taken as critical quality attributes (CQAs). Optimization with response surface method clarified the relationship between X1, X2 and CQAs, and design space was established based on the constraints set on the responses. The optimized batch with concentration of soya lecithin 2gm and ethanol 30ml was subjected to ultrasonication using Probe Sonicator to form nanoparticulate ethosomal dispersion. This Ethosomal vesicles showed a mean particle size of 63.78 nm, zeta potential -41.2 mV and %EE 81.54%. SEM studies revealed 3-Dimensional nature of Ethosomes with smooth surface. DSC, results exhibited entrapment of Miconazole Nitrate in Ethosomes. Ethosomes were loaded into cream-o-gel (CG1-CG5) using
concentration 2.5%, 3%, 3.5%, 4%, 4.5% w/v of polymer Simulgel INS 100. CG3 formulation showed enhanced % cumulative drug release (67.95±0.25%) in comparison to plain drug cream-o-gel (35.91±0.47%) after 6 hrs. Texture analysis results showed the formulation to be less sticky and having good spread ability. It showed potential antifungal activity against Calbicans in comparison to marketed cream and did not cause any skin irritation on healthy wistar rats. Results suggested ethosomes asefficient carriers for Miconazole Nitrate topical delivery.