盐酸尼卡地平β晶型制备及其固体分散体研究  

Preparation of nicardipine hydrochloride β crystal type and its solid dispersion

作　　者：盛巍 王洪亮 杨艳芳 汪仁芸 夏学军 李琳 金笃嘉 叶军 刘玉玲 SHENG Wei;WANG Hong-liang;YANG Yan-fang;WANG Ren-yun;XIA Xue-jun;LI Lin;JIN Du-jia;YE Jun;LIU Yu-ling(Institute of Materia Medica, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Beijing 100050)

机构地区：[1]中国医学科学院北京协和医学院药物研究所&药物传输技术及新型制剂北京市重点实验室,北京100050

出　　处：《中南药学》2018年第6期731-737,共7页Central South Pharmacy

摘　　要：目的制备盐酸尼卡地平(Nic)β晶型,实现与原研产品晶形一致;探讨固体分散体技术对Nic溶解度的改善效果。方法采用丙酮重结晶法制备Nic原料药并进行化学纯度、熔点和晶型检测;以PVP K30、PEG6000、普朗尼克F68为载体材料,制备Nic固体分散体,考察载体材料用量及其对溶解度的影响,采用示差扫描量热、X射线粉末衍射、傅里叶变换红外光谱进行物相鉴别和作用机制探讨。结果制得的Nic原料药,熔点为169.2~171.2℃,化学纯度>99.3%,特征衍射峰与文献报道完全一致。3种载体均可与Nic通过分子间相互作用形成固体分散体,药物由晶态转变为无定型态,当Nic/载体为1∶3时,溶解度由11 mg·m L^(-1)提高至160 mg·m L^(-1)。结论成功制备了与原研一致的β晶型Nic,采用固体分散体技术,Nic溶解度可显著改善,为后续渗透泵控释制剂研发提供了良好的中间载体。Objective To prepare nicardipine hydrochloride （Nic） β crystal type to ensure consistency with the crystal form of original product, and to determine the effect of solid dispersion technology on the improvement of the Nic solubility. Methods Nic was prepared by acetone recrystallization method. Then it was characterized by HPLC to detect the chemical purity, melting point test, X ray powder diffraction and differential scanning calorimetry. Nic solid dispersion was acquired with PVP K30, PEG6000, and poloxamer F68 as the carrier materials. The solubility of Nic was measured and phase identification was conducted with differential scanning calorimetry, X-ray powder diffraction, and fourier transform infrared spectrum. Results The melting point of prepared Nic was 169.2 - 171.2 ℃ and chemical purity of Nic was more than 99.3%. The characteristic diffraction peaks were in complete accordance with literature reports. All three carriers formed Nic solid dispersions in the amorphous state. The solubility of Nic increased to 160 mg · mL^-1 from 11 mg · mL^-1, with Nic and carrier at 1：3. Conclusion Nic β crystal type is prepared successfully and is consistent with the original preparation. The solid dispersion technology significantly improves the solubility of Nic, which provides precondition for the subsequent research and development of osmotic pump controlled release preparation of Nic.

关 键 词：盐酸尼卡地平 Β晶型 固体分散体 一致性 溶解度 

分 类 号：R943[医药卫生—药剂学]