女贞子三萜-胡椒碱共无定型复合物的表征和体外溶出度评价  

Characterization of co-amorphous complex with piperine and triterpenoids from Ligustri Lucidi Fructus and dissolution evaluation in vitro

作　　者：余丹妮[1] 伍薇 祁玮玮 王如意 刘双双[1] 李俊松[2] 

机构地区：[1]中国药科大学生物功能性材料重点实验室,江苏南京211198 [2]南京中医药大学江苏省中药炮制重点实验室,江苏南京210046

出　　处：《中草药》2018年第3期561-568,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81403118)

摘　　要：目的制备女贞子三萜(triterpenoids of Ligustri Lucidi Fructus,TLLF)-胡椒碱(piperine,PIP)共无定型复合物(co-amorphous complex,CAC),以提高TLLF的溶出度。方法采用溶剂挥发法制备TLLF-PIP-CAC,运用粉末X射线衍射(PXRD)、差示扫描量热法(DSC)、扫描电子显微镜(SEM)对TLLF-PIP-CAC的微观结构进行表征,通过热稳定性实验考察TLLF-PIP-CAC的稳定配比,采用紫外-可见分光光度法(UV-Vis)和高效液相色谱法(HPLC)分别测定TLLF、PIP及TLLF-PIP-CAC中齐墩果酸(OA)和熊果酸(UA)或PIP的药物量,运用傅里叶红外光谱(FTIR)对优选的TLLF-PIP-CAC各组分间的相互作用进行分析,并对其溶解和体外溶出行为进行考察,以评价制剂的形成。结果 PXRD结果表明,TLLF-PIP质量比为1∶1的TLLF-PIP-CAC为稳定的CAC。SEM图谱表明TLLF-PIP-CAC粒子呈类球形。FTIR图谱提示,TLLF主要分子及PIP分子间存在氢键相互作用。溶解和体外溶出实验表明,TLLF在TLLF-PIP-CAC中的溶解和溶出均显著提高,而PIP的溶出显著降低,两者呈现伴随释放效应。结论所制备的TLLF-PIP-CAC能显著提高TLLF的溶出度和CAC稳定性,这一制剂为促进难溶性中药组分的复方配伍提供了一定的参考。Objective To prepare a co-amorphous complex of piperine（PIP） and triterpenoids from Ligustri Lucidi Fructus（TLLF） to improve the dissolution of TLLF. Methods TLLF-PIP co-amorphous complex was prepared using solvent evaporation method. The microscopic structure of co-amorphous complex（CAC） was analyzed using differential scanning calorimetry（DSC）, scanning electronmicroscopy（SEM）, and powder X-ray diffraction（PXRD）, the optimal ratio of the two components was investigated through the thermal stability experiment. Ultraviolet-visible spectrophotometry（UV-Vis） and high performance liquid chromatography（HPLC） were applied to determine the amount of TLLF, PIP and the individual components, ursolic acid（UA） and oleanolic acid（OA）, respectively. The interaction of the optimal CAC was analyzed by Fourier transform infrared spectroscopy（FTIR）, and its solubility and dissolution behavior in vitro were also studied to evaluate the formation of the preparation. Results PXRD analysis indicated that the TLLF-PIP-CAC with a mass ratio of 1∶1 exhibited a stable amorphous state, which particles presented in near-spherical shape. FTIR results indicated that there are some hydrogen interactions between the moleculars of TLLF and PIP. The solubility and dissolution determination exhibited a pairwise released behavior with improved triterpenoids and decreased piperine dissolution. Conclusion The prepared TLLF-PIP-CAC can significantly improve the dissolution and amorphous stability of TLLF, which may provide a reference for the compatibility of insoluble compound in traditional Chinese medicine.

关 键 词：女贞子三萜 胡椒碱 共无定型复合物 溶出 伴随释放 复方配伍 熊果酸 齐墩果酸 

分 类 号：R283.6[医药卫生—中药学]