Optimization, characterization and in vitro/vivo evaluation of azilsartan nanocrystals

Azilsartan (AZL), a poorly soluble drug, was considered to be fit for nanocrystals to improve its solubility. Our study intended to prepare AZL nanocrystals by means of bead milling method. Eight stabilizers or their binary combination and the milling time were set to be variable factors to optimize AZL nanosuspension formulation, and six types of freeze-drying supports were investigated to reduce the aggregation of particles during the solidification. AZL nanocrystals with or without sodium deoxycholate (NaDC) as combined stabilizer with Poloxamer 188 (F68) were prepared owning mean particle sizes of about 300 nm and 460 nm. During the screening processes, the formulation containing NaDC showed a smaller particle size and better stability during lyophilization. The irregular shape and crystal form changing in AZL nanocrystals were discovered by various characterizations. And with physical mixture as reference, nanocrystals showed its improvement about in-vitro dissolution and in-vivo bioavailability. In conclusion, the nanocrystals of AZL could be prepared well in our study. Additionally, our results suggested that NaDC was an appreciated excipient on the nanocrystals platform, which can exhibit the abilities of size-reduction and stability-maintaining on freeze-drying.

Graphical AbstractThrough formulation screening, the irregular-shaped azilsartan nanocrystals were prepared and optimized by bead milling method and solidified by freeze-drying. The best formulation which had the size of 300 nm was expressed in its state by the studies of morphology and crystal from. And azilsartan nanocrystals showed its improvement about in-vitro dissolution and in-vivo bioavailability with physical mixture as reference.78