聚乙烯吡咯烷酮抑制葛根素一水合物在溶出过程中向二水合物的转变

Inhibition of transformation from puerarin monohydrate to puerarin dihydrate by polyvinylpyrrolidones during dissolution

葛根素为异黄酮类化合物,具有抗炎、抗氧化及神经保护的作用,目前临床上主要用于心脑血管疾病。本文报道了市售葛根素原料药为一水合物,且该一水合物在饱和溶出过程中葛根素浓度经平台期后显著下降至另一个低的平台。为揭示该现象的内在原因,对溶出后的剩余固体进行粉末X射线衍射(PXRD)、热重分析和卡尔费休水分测定,结果表明剩余固体为水溶性更低的葛根素二水合物。此外,还考察了在溶出介质中加入聚乙烯吡咯烷酮类聚合物(PVPK12、PVPK30和PVPK90)对葛根素一水合物向二水合物转变的影响,结果表明聚合物可抑制该转变,使溶出过程中葛根素浓度维持在更高的水平。

Puerarin（PUE）,an isoflavone with anti-inflammation,anti-oxidation and neuroprotection effects,has been widely applied to the treatment of cardiovascular diseases in clinics in China. In the current study,we reported that the active pharmaceutical ingredient（API） of marketed products was the PUE monohydrate（PUEMH）. During its supersaturated dissolution,the PUE concentration quickly reached a plateau,followed by a gradually concentration decrease to another lower plateau. In order to explore the internal mechanism of above phenomenon,the solid residues after saturated dissolution test were characterized by powder X-ray diffraction（PXRD）,thermal gravity analysis（TGA） and Karl Fisher titration（KFT）. PXRD suggested that a novel PUE crystal different from PUEMH formed during its dissolution,the following TGA and KFT confirmed the generation of PUE dihydrate（PUEDH） with much lower solubility. Moreover,polyvinylpyrrolidones（PVPK12,PVPK30 and PVPK90） were added in the dissolution medium to investigate their potential inhibition effects on such crystal transformation during dissolution process. We observed that polymers could inhibit the transformation from PUEMH to PUEDH and result in much higher PUE concentration level than that in pure water.