不同载体木犀草素固体分散体的制备及溶出度测定

Preparation and in vitro dissolution determination of luteolin solid dispersion with different vehicles

目的:制备不同载体的木犀草素(LUT)固体分散体(SD),提高LUT的溶解度和溶出度,并探讨不同载体对药物溶解度和溶出度的影响。方法:应用平衡溶解度和超饱和溶液抑晶试验,筛选合适的载体材料并采用溶剂法制备SD;在单因素试验基础上,以药载比、温度和乙醇用量为影响因素,溶出度为指标,采用Box-Behnken设计优化处方和工艺;用差式扫描量热法(DSC)、扫描电镜(SEM)、X-射线衍射(XRD)以及傅里叶红外光谱(FTIR)对SD进行表征。结果:选择聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(Soluplus®)和共聚维酮(PVP/VA)为载体材料;最优条件为药载比1∶11,温度60℃,乙醇用量50 mL(Soluplus®)或35 mL(PVP/VA);与原料药相比,2种SD溶解度分别提高42倍(Soluplus®)和102倍(PVP/VA);120 min时2种SD的累积溶出度均达到95%;SEM、DSC和XRD表征结果显示,药物在SD中均以无定形态存在;IR结果显示,药物与载体之间存在氢键作用。结论:2种载体制备的SD均能提高LUT的溶解度和溶出度,其中载体对提高LUT溶解度能力大小为PVP/VA>Soluplus®,但溶出度无明显差异。

OBJECTIVE To prepare luteolin(LUT)solid dispersion(SD)with different vehicles in order to improve the solubility and dissolution of LUT,and to discuss the effects of different vehicles on drug solubility and dissolution.METHODS Equilibrium solubility and supersaturated solution crystallization inhibition tests were applied to screening suitable vehicle materials,and SD was prepared by a solvent method.On the basis of single factor test,and with drug loading ratio,temperature and ethanol amount as the influencing factors,Box-Behnken design was used to optimize the formulation and process with dissolution as the index.SD was characterized by differential scanning calorimetry(DSC),scanning electron microscopy(SEM),X-ray diffraction(XRD)and Fourier transform infrared spectroscopy(FTIR).RESULTS Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer(Soluplus®)and copovidone(PVP/VA)were selected as the vehicle materials to prepare SD.The optimal conditions were determined as follows:drug loading ratio of 1∶11,temperature at 60℃,ethanol amount of 50 mL(Soluplus®)or 35 mL(PVP/VA).Compared with the bulk drug,the solubility increased by 42 times(Soluplus®)and 102 times(PVP/VA),respectively,and the cumulative dissolution rate of both SD reached 95%at 120 min.The results of SEM,DSC and XRD showed that the drug existed in an amorphous state in SD,and FTIR results showed that there were hydrogen bonding between the drug and the vehicles.CONCLUSION Both SD prepared by the two vehicles could improve the solubility and dissolution of LUT,and the LUT solubility increase effect by the vehicles was PVP/VA>Soluplus®,while there was no significant difference between them.