Title:Ursolic Acid Nanocrystals for Dissolution Rate and Bioavailability Enhancement: Influence of Different Particle Size
Volume: 13
Issue: 8
Author(s): Jiaxin Pi, Zhidong Liu, Hao Wang, Xing Gu, Shuya Wang, Bing Zhang, Hansen Luan and Zhuangzhi Zhu
Affiliation:
Keywords:
Dissolution rate, high pressure homogenization, nanocrystals, nanosuspensions, oral bioavailability, ursolic acid.
Abstract: Background: Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to
possess a variety of pharmacological activities, but the poor oral bioavailability of UA owing to the
poor aqueous solubility and membrane permeability limits the further clinical application.
Objective: The purpose of the present study was to develop UA nanocrystals and microcrystals employing
high pressure homogenization (HPH) and to evaluate their effects on UA oral bioavailability.
Method: The crystalline morphology of UA nanocrystals and microcrystals prepared by HPH was observed
by scanning electron microscopy and the crystalline state was characterized by differential scanning
calorimetry (DSC) and powder X-ray diffraction (PXRD). The dissolution rate of UA nanocrystals
in different pH conditions was tested. Oral bioavailability of UA nanocrystals and microcrystals comparing
with UA coarse suspension was evaluated in SD rats after 50 mg·kg-1 administration.
Results: UA nanocrystals and microcrystals, the size of which ranged between 291.7 nm and 1299.3 nm
were obtained. The results of DSC and PXRD revealed a degree of crystalline-amorphous transformation
during HPH preparation. A significant increase was observed in the dissolution rate of UA nanocrystals.
The relative bioavailability of UA nanocrystals and microcrystals exhibited 2.56 and 1.40-fold
enhancement than that of UA coarse suspension, respectively, along with an increased peak concentration
and a prolonged retention.
Conclusion: The nanosized UA crystal is a viable and efficient approach to improve the oral bioavailability
of UA.
