兰索拉唑-β-环糊精包合物探究.docVIP

兰索拉唑-β-环糊精包合物探究[摘要] 目的:研究β-环糊精(β-CD)对难溶药物兰索拉唑(LPZ)的包合作用。方法:采用共蒸发法(CE)和喷雾干燥法(SD)按照LPZ∶β-CD的摩尔比为1∶1的比例制备LPZ-β-CD包合物,利用差示扫描量热法(DSC)和傅立叶红外光谱法(FTIR)对SD法制备的包合物进行结构表征,并进行溶出度测定。结果:药物的部分基团已进入β-CD空腔形成了包合物,CE法和SD法制备的包合物溶出均优于LPZ与β-CD的物理混合物。结论:β-CD能明显提高LPZ的溶解度和溶出度。 [关键词] β-环糊精;兰索拉唑;包合物;溶出度 [中图分类号] R943[文献标识码]A [文章编号]1673-7210(2010)04(a)-099-03 Study on Lansoprazole-β-Cyclodextrin Inclusion Complexes LI Zhen1, HAO Tangna2, DING Pingtian3*, TIAN Yan1,TIAN Ge1,LIU Kexin1 (1.School of Pharmacy, Dalian Medical University, Dalian 116044, China; 2.Department of Pharmacy, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China; 3.School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China) [Abstract] Objective: To investigate the complexation of lansoprazole (LPZ) with β-cyclodextrin (β-CD). Methods: Solid inclusion complexes of LPZ with β-CD, prepared by co-evaporating method (CE) and spray drying method (SD) at mole ratios of 1∶1 (drug to CD) were studied preliminarily by differential scanning calorimetry (DSC). Fourier transform infrared (FTIR) spectroscopy and in vitro dissolution test. Results: According to the information obtained from DSC and FTIR, it could be concluded that there were interactions between the drug and β-CD, which could led to a rapid increase in the amount of dissolved drug in pH 6.8 buffer solution. Conclusion: The solubility and dissolution rate of LPZ are improved by β-CD complexation obviously. [Key words] β-CD; Lansoprazole; Inclusion complexes; Dissolution 质子泵抑制剂是目前治疗消化性溃疡最先进的一类药物。其抑酸的主要机制:人体在受体和第二信使的作用下,位于胃壁细胞分泌管上的H+/K+-ATP酶分解ATP获得能量,通过H+/K+转运机制,将胞浆内H+泵入胃腔,再与Cl-形成胃酸。其中质子泵是胃酸分泌过程中的重要环节,抑制H+/K+-ATP酶的活性即可阻断由任何刺激引起的胃酸分泌[1-3]。兰索拉唑(lansoprazole,LPZ)为质子泵抑制剂中的代表性药物,与奥美拉唑相比,其结构中引入了三氟乙氧基,亲脂性增加,可更迅速地透过壁细胞发挥药效[4]。LPZ结构中含亚硫酰基,对湿、热较敏感,随pH降低稳定性变差。LPZ属于低溶解度、高渗透类药物,溶出速率是影响其吸收的限速步骤[5]。包合技术是一种常用的制剂学手段,可增加药物溶解度,提高药物稳定性,掩盖药物不良气味等[6]。本实验拟将兰索拉唑制成β-环糊精包合物,以期增加其溶解度和溶出速率。 1 仪器与试药 1.1 仪器 高效液相色谱仪(日本Shimadz