两种介孔二氧化硅载体用于改善西洛他唑溶出度的比较  

Comparison on two types of mesoporous silica in enhancing the dissolution of cilostazol

作　　者：王彦竹[1,2] 赵勤富[2] 孙清[3] 李乐道[2] 姜同英[2] 王思玲[2] 

机构地区：[1]天津药物研究院,天津300193 [2]沈阳药科大学药学院,辽宁沈阳110016 [3]沈阳药科大学医疗器械学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2014年第1期1-8,共8页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81072605);沈阳市人才资源开发专项资金资助项目

摘　　要：目的研究两种介孔二氧化硅(MCM-48和MCM-41)作为西洛他唑(cilostazol,CLT)的载体在改善药物溶出度方面的作用。方法分别采用3种方法制备CLT/MCM-48和CLT/MCM-41固体分散体,以紫外分光光度法测定样品的载药量。以溶出度为评价指标,对载药方法、药物与载体的质量比和固体分散体粒径等因素进行了优化,并应用氮气吸附和低温DSC法分析样品中药物的存在状态。结果当药物与载体质量比为1∶3时,以共沉淀法制备的CLT/MCM-48和CLT/MCM-41样品,经150μm孔径筛处理后,药物的溶出度最高,分别达到78%和85%。与以PEG4000为载体制备的CLT/PEG相比,显示了更加优良的药物溶出的稳定性。氮气吸附结果表明药物已经成功分散于载体孔道中;DSC分析显示,药物极有可能以无定形存在,且介孔孔道对药物向稳定型转变有延缓和阻滞作用。结论 MCM-48和MCM-41作为药物载体制备固体分散体能够不同程度地提高CLT的溶出度。Objective To investigate two types of mesoporous silica （MCM-41 and MCM-48 ） as solid dis- persion carders to improve the drug dissolution of cilostazol. Methods Cilostazol （CLT） as a model drug was loaded into MCM-41 and MCM-48 by three common drug-loading methods. The drug contents of the CLT/MCM-41 and CLT/MCM-48 were measured by UV method. Taking dissolution as the evaluation cri- teria, the effect of drug loading methods, proportion of the drug and the carder and powder particle size on solid dispersion dissolution behaviors was systematically studied. Low temperature differential scanning calorimetry （DSC） was applied to analyze the state of cilostazol in the samples. Results The best dissolution rate was obtained when CLT/MCM-41 and CLT/MCM-48 samples were prepared by co-precipitation with the drug and carder ratio of 1：3 after 150 μm-mesh sieve treatment. Compared with the classic solid dispersion CLT/PEG, samples prepared by mesoporous silica carder possessed better stability on dissolution profiles. The results of nitrogen adsorption illustrated that the drug was successfully dispersed into the pore structure. The DSC results showed that the drug was most likely to exist in an amorphous state in the nanopores, which could slow down and even prevent the crystalline transition. Conclusions The solid dispersion prepared with MCM-41 and MCM-48 can improve drug dissolution to varying degrees.

关 键 词：介孔二氧化硅 MCM-41 MCM-48 西洛他唑 固体分散体 溶出度 

分 类 号：R94[医药卫生—药剂学]