Preparation and Optimization of Amorphous Ursodeoxycholic Acid Nano-suspensions by Nanoprecipitation based on Acid-base Neutralization for Enhanced Dissolution.
BACKGROUND
Ursodeoxycholic acid, usually used to dissolve cholesterol gallstones in clinic, is a typical hydrophobic drug with poor oral bioavailability due to dissolution rate-limited performance. The objective of this study was to increase the dissolution of ursodeoxycholic acid by amorphous nanosuspensions.


METHODS
Nanoprecipitation based on acid-base neutralization was used to prepare the nanosuspensions with central composite design to optimize the formula. The nanosuspensions were characterized by particle size, morphology, crystallology and dissolution.


RESULTS
The ursodeoxycholic acid nanosuspensions showed mean particle size around 380 nm with polydispersion index value about 0.25. Scanning electron microscope observed high coverage of HPMC-E50 onto the surface of the nanosuspensions. Differential scanning calorimetry and powder X-ray diffractometry revealed amorphous structure of the ursodeoxycholic acid nanosuspensions. A significant increase of dissolution in acidic media was achieved by the amorphous nanosuspensions compared with the physical mixture.


CONCLUSIONS
It can be predicted that the amorphous nanosuspensions show great potential in improving the oral bioavailability of ursodeoxycholic acid.
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Yike
Y
Xie
Shanghai Dermatology Hospital, Shanghai 200443, China.
Zhongjian
Z
Chen
Shaanxi Academy of Traditional Chinese Medicine, Xi'an 710003, China.
Rui
R
Su
Shaanxi Academy of Traditional Chinese Medicine, Xi'an 710003, China.
Ye
Y
Li
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Jianping
J
Qi
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Wei
W
Wu
Department of Pharmaceutics, School of Pharmacy, Fudan University, P.O. Box: 201203, Shanghai, China.
Yi
Y
Lu
D000284:Administration, Oral; D001682:Biological Availability; D065546:Drug Liberation; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013535:Suspensions / Q000737:chemistry*; D014580:Ursodeoxycholic Acid / Q000737:chemistry*; D014961:X-Ray Diffraction
D013535:Suspensions; D014580:Ursodeoxycholic Acid
Acid-base neutralization; amorphous; dissolution; nanosuspensions; oral bioavailability; ursodeoxycholic acid