QbD Based Approach to Enhance the In-Vivo Bioavailability of Ethinyl Estradiol in Sprague-Dawley Rats.

Lyophilized nanosuspension of poorly soluble Ethinyl estradiol (EE) was fabricated to enhance its solubility and bioavailability using a quality-by-design (QbD) approach. With the help of the Ishikawa diagram, prospective risk factors were identified and screened by Placket-Burman design to investigate the effects of formulation and process variables on dependent variables. The number of cycles (X4), the concentration of soya lecithin (X5) and the concentration of tween 80 (X7) were identified as significant factors (P<0.05), which were further optimized using Central Composite Design. The mean particle size, zeta potential, drug content and entrapment efficiency of optimized lyophilized EE nanosuspension (EENPs) was 220±0.37 nm, -19.3±6.73 mV, 92.23±0.45%, 99.52±0.52%, respectively. Significantly, EENPs enhances Cmax and AUC0-t by 1.5, 1.7 folds and relative bioavailability by 2-fold with its distribution being at higher concentrations in the liver, spleen, and stomach. Thus, QbD based approach for the development of nanosuspension could be an absolute, optimistic approach to identify the critical process parameters and critical quality attributes.