Pharmaceutical and pharmacokinetic characteristics of different types of fenofibrate nanocrystals prepared by different bottom-up approaches

Abstract

Low dissolution rate of a poorly water soluble drug often leads to low and variable oral bioavailability. Formulating drugs as nanocrystals can help to overcome these problems by increasing the solubility and dissolution velocity. But different preparation approaches may result in different nanocrystals with different characteristics. In this study, three types of fenofibrate nanocrystals (FNT-NCs) were prepared by bottom-up methods, antisolvent and thermal precipitation under different conditions. These FNT-NCs were characterized by scanning electron micrography, dissolution testing, differential scanning calorimetry and powder X-ray diffractometry. A significant increase of dissolution rate was observed in the drug nanocrystals compared to the crude FNT powder (from 20% to 80% in 5 min). The crystallinity of the FNT-NCs prepared by antisolvent precipitation increased slightly, while that by thermal precipitation decreased. The oral bioavailability of two types of FNT-NCs prepared by antisolvent precipitation in rats increased notably compared to that of the crude powder (5.5-folds and 5.0-folds, respectively). However, the oral absorption of FNT-NCs prepared by thermal precipitation did not increase, although its dissolution rate was higher than that of the crude powder. In conclusion, different bottom-up methods produce different FNT-NCs with different crystallinity, which results in different oral bioavailability. Namely, a careful study and rational choice on preparation approaches are significant for the nanocrystal techniques.