A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein

Abstract

Baicalein (BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide (BE-NCT) nano-cocrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0 − t of BE-NCT nano-cocrystals (6.02-fold) was significantly higher than BE coarse powder (1-fold), BE-NCT cocrystals (2.87-fold) and BE nanocrystals (3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BE-NCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations. Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.