title: Ursolic Acid Nanocrystals for Dissolution Rate and Bioavailability Enhancement: Influence of Different Particle Size.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The nanosized UA crystal is a viable and efficient approach to improve the oral bioavailability of UA.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Pi
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China, P.O. Box: 300193. lonerliuzd@163.com.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China, P.O. Box: 201203. wanghao99@hotmail.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Gu
authors.forename: Shuya
authors.initials: S
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Hansen
authors.initials: H
authors.lastname: Luan
authors.forename: Zhuangzhi
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D016503:Drug Delivery Systems; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D033362:Powder Diffraction; D011312:Pressure; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014315:Triterpenes / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014961:X-Ray Diffraction; D000097245:Ursolic Acid
chemical_list: D014315:Triterpenes; D000097245:Ursolic Acid