Optimization of apigenin nanoparticles prepared by planetary ball milling: In vitro and in vivo studies

This study intended to optimize apigenin (APG) nanoparticle formulation prepared by planetary ball milling to enhance its dissolution rate and bioavailability using a design of experiment (DoE). In this study, polyvinyl pyrrolidone (PVP K30) was used as a nanoparticle stabilizer. The independent parameters of milling speed, milling ball size, and drug to solvent ratio were evaluated for their impacts on APG nanoparticles concerning the nanoparticle size (Y1), zeta potential (Y2), and drug dissolution efficiency after 60 min, notated as % DE60 (Y3). The milling ball size showed a significant antagonistic effect (P = 0.0210) on the size of APG nanoparticles, while milling speed had an agonistic effect on the zeta potential values of drug nanoparticles, ranging from low to medium speed levels. In addition, ANOVA analysis indicated that the effect of the drug-to-solvent ratio on the % DE60 of APG from the nanoparticle formulations was antagonistically significant (P = 0.015), and the quadratic effect of milling speed (AA) also had a significant antagonistic effect (P = 0.025) on the % DE60. Risk assessment analytical tools revealed that milling ball size and milling speed significantly affect the nanoparticle size. The drug/solvent ratio exerted a strong impact on % DE60. Furthermore, the maximum plasma concentration (C (max)) of the optimized APG nanoparticle formula increased by four folds. In addition, AUC(0-t) (ng.mL(-1) .h(-1)) for APG nanoparticle (353.7 +/- 185.3 ng.mL(.)(-1)h(-1)) was higher than that noticed in the case of the untreated drug (149 +/- 137.5 ng.mL(--1)) by more than two folds.