Effects of Crystal Form on in vivo and in vitro Behavior of Astilbin Nanosuspensions / 中国药房

ABSTRACT

OBJECTIVE： To investigate the effects of crystal form on in vivo and in vitro behavior of Astilbin nanosuspensions （AT-NS）. METHODS： AT-NS1 and AT-NS2 were prepared by precipitation method and miniaturized media milling method respectively. The particle size and polydispersity index （PDI） were determined by laser particle size analyzer. X-ray diffraction （XRD）， scanning electron microscopy （SEM）， HPLC and paddle method were used to analyze and compare the structure characteristics， appearance morphology and in vitro dissolution of AT raw material， AT-NS1 and AT-NS2. Totally 15 healthy male SD rats were randomly divided into AT raw material， AT-NS1 and AT-NS2 group， with 5 rats in each group. They were given relevant medicine suspension 120 mg/kg （using water as solvent） intragastrically； blood samples  were collected from orbit before medication （0 min） and 5， 10， 20， 30， 60， 120， 240， 480 min after medication. Using rutin as internal standard， HPLC method was used to determine plasma concentration of AT in rats. Pharmacokinetic parameters were calculated by using DAS 2.0 software and then compared. RESULTS： The particle sizes of AT-NS1 and AT-NS2 were （212.48±0.32） nm and （226.36±2.29） nm， respectively； PDI were 0.129 3±0.026 3 and 0.254 7±0.012 4. XRD analysis showed AT-NS1 was amorphous， and AT-NS2 was crystalline. Diffraction peaks of both were different from those of AT raw material. SEM analysis showed that AT-NS1 and AT-NS2 were similar in morphology， and they were spherical and uniform in size； AT raw material was lump with large particle size and different sizes. Results of dissolution tests showed that accumulative dissolution of AT raw material， AT-NS1 and AT-NS2 were 4.54％， 35.01％， 12.22％ at 1 h； accumulative dissolution of them were 24.01％， 81.14％， 64.69％ at 12 h； accumulative dissolution of them were 36.04％， 84.47％， 85.86％ at 24 h， respectively. Results of pharmacokinetic study showed， compared with AT raw material group， cmax and AUC0-∞ of AT-NS1 and AT-NS2 groups as well as t1/2z of AT-NS1 group were increased significantly， while tmax of AT-NS1 group was significantly reduced significantly （P＜0.05）. Compared with AT-NS2 goup， cmax， AUC0-∞ and t1/2z of AT-NS1 group were increased significantly， while tmax was reduced significantly （P＜0.05）. CONCLUSIONS： When AT is prepared into NS， dissolution in vitro and oral absorption in vivo of AT are increased significantly. In a short time， the dissolution/absorption of amorphous NS is faster than crystalline NS.