title: Formulation and pharmacokinetics evaluation of puerarin nanocrystals for intravenous delivery.
abstract: Puerarin is a very widely used drug for treating coronary heart disease. Owing to its poor water solubility and the adverse drug reactions caused by cosolvents having been confirmed by SFDA, the aim of present study was to construction and evaluation the puerarin nanocrystals in vitro and in vivo. The nanocrystals prepared were characterized using PCS, AFM, TEM, SEM and DSC. For the assessment of the pharmacokinetic parameters the developed formulations have been intravenous administered to beagle dogs. Results revealed that a narrow size distributed nanocrystals composed of crystallized spherical particles with a mean particle size of 423.6 +/- 17.3 nm, a poly-dispersity index of 0.13 +/- 0.07 and a negative charges around -30 mV was obtained. Puerarin dissolution velocity and saturation solubility were enhanced by the nanocrystals. DSC analysis revealed that the crystallinity of the puerarin was preserved during the high pressure homogenization and freeze-drying processes. Administration of the nanocrystals led to a mean plasma profile with almost similarly low variations in comparison to the reference solution, however with no initial blood peak as observed with the solution formulation. The puerarin nanocrystals exhibited a significantly (P < 0.05) reduced Cmax and clearance, and a significantly (P < 0.05) greater MRT, clearance and elimination half-life compared to the puerarin solution. These results revealed the opportunity to formulate puerarin in nanocrystals for intravenous delivery with higher safety.
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Shandong Polytechnic University, Jinan 250353, China.
authors.forename: Yancai
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.forename: Yingying
authors.initials: Y
authors.lastname: Ma
authors.forename: Yongli
authors.initials: Y
authors.lastname: Du
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Liu
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D007275:Injections, Intravenous; D007529:Isoflavones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility
chemical_list: D007529:Isoflavones; C033607:puerarin