Surface Stabilized Efavirenz Nanoparticles for Oral Bioavailability Enhancement

The aim of the present study was to prepare surface stabilized nanoparticles for oral bioavailability enhancement of efavirenz (EFZ). EFZ nanoparticles (EFZ-NPs) were prepared by combination of anti-solvent precipitation and high pressure homogenization technique, using hydroxy propyl methyl cellulose as stabilizer which resulted in formation of EFZ-NPs of average particle size ∼350 nm with excellent particles size distribution (<0.2). EFZ-NPs were freeze dried using trehalose as cryoprotectant and found to be quite stable against storage at 25 ± 2 °C/60 ± 5% RH and 40 ± 2 C/75 ± 5% RH as evidenced from particle size, particle size distribution and drug content. EFZ-NPs demonstrated an increase in saturation solubility by 5.16 folds in comparison with free EFZ. In vitro dissolution studies established advantage of EFZ-NPs over free EFZ as more than 75% drug was dissolved within 5 min in case of EFZ-NPs while it was approx 20% in case of free EFZ. In vivo pharmacokinetic studies further confirmed the potential of EFZ-NPs as 2.02 folds increase in peak plasma concentration and 2.29 folds increase in AUC_0–∞ were observed in comparison to free EFZ. The In vitro–In vivo relationship of the formulations further suggested higher correlation coefficient of 0.9995 for EFZ-NPs in Levys plot as compared to 0.8726 for free EFZ.