title: A novel high-pressure precipitation tandem homogenization technology for drug nanocrystals production - a case study with ursodeoxycholic acid.
abstract: To overcome the limitations of the conventional particle size reduction technologies, a novel combinative particle size reduction method for the effective production of homogeneous nanosuspensions was investigated. Ursodeoxycholic acid, a poorly soluble drug representative, was tried to prepare nanosuspension by homogenization technology and high-pressure precipitation tandem homogenization technology. It was shown that the combinative approach could significantly improve the particle size reduction effectiveness over conventional homogenization approach. The Box-Behnken design analysis for process optimization revealed that the acceptable UDCA-NS was obtained wherein the optimal values of A, B, C and D were 10%, 500 bar, 0.125 and 600 bar, respectively. SEM results demonstrated that no significant aggregation or crystals growth could be observed in the freeze-dried UDCA nanocrystals. The DSC and XRD results showed that UDCA remained in a crystalline state. Dissolution velocities of the freeze-dried UDCA-NS powder were distinctly superior compared to those of the crude powder and physical mixture. The high-pressure precipitation tandem homogenization technology can be a good choice for nanosuspension preparation of poorly soluble UDCA, due to high efficiency of particle size reduction.
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine , Nanchang , China and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Yue
authors.forename: Peng-Yi
authors.initials: PY
authors.lastname: Hu
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Yuan
mesh_terms: D011232:Chemical Precipitation; D005612:Freeze Drying / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D011312:Pressure; D012995:Solubility; D013535:Suspensions / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014580:Ursodeoxycholic Acid / Q000737:chemistry*
chemical_list: D011208:Powders; D013535:Suspensions; D014580:Ursodeoxycholic Acid