2种晶型酒石酸唑吡坦的体外固有溶出速率和渗透性检测  

Determination of Intrinsic Dissolution Rate and Permeability of Two Crystal Forms of Zolpidem Tartrate in vitro

作　　者：时晓燕 王延华 王楠 潘增玉 冯中 SHI Xiaoyan;WANG Yanhua;WANG Nan;PAN Zengyu;FENG Zhong(Shandong Engineering Research Center for New Drug Pharmaceuticals R&D in Shandong Province,Lunan Better Pharmaceutical Co.,Ltd.,Linyi 273400;School of Pharmaceutical Sciences,Shandong University of Traditional Chinese Medicine,Jinan 250355)

机构地区：[1]鲁南贝特制药有限公司,药物新制剂研发山东省工程研究中心,山东临沂273400 [2]山东中医药大学药学院,山东济南250355

出　　处：《中国医药工业杂志》2024年第5期680-685,共6页Chinese Journal of Pharmaceuticals

基　　金：泰山产业领军人才项目(tscx202306086)。

摘　　要：分别考察了2种晶型酒石酸唑吡坦(1)(晶型A和晶型D)的溶解和溶出特性。首先,通过XRD和DSC法确证2种晶型1具有不同晶体结构和热力学特性。随后分别测定了晶型A和晶型D在不同pH值介质(水、0.01 mol/L盐酸、pH 4.5乙酸盐缓冲液和pH 6.8 PBS)中的表观溶解速率和固有溶出速率。结果显示,2种晶型1在pH 6.8 PBS中的表观溶解速率、表观溶解度和固有溶出速率有较大差异。根据所得结果,2种晶型都表现出高溶解特性。平行人工膜渗透试验结果显示,1的有效渗透系数为8×10^(–5)~9×10^(–5)cm/s,提示其渗透性强。该研究显示,2种晶型1的溶解和溶出速度、晶体结构和熔点都具有一定差异,但都分类为BCSⅠ类药物,可为制剂研发中原料药的晶型筛选提供依据。The solubility and dissolution characteristics of two crystal forms(A and D)of zolpidem tartrate(1)were investigated.Firstly,the two crystal forms were characterized by XRD and DSC.The results showed that they had different crystal structures and thermodynamic properties.Subsequently,the apparent dissolution rates and intrinsic dissolution rates of crystal forms A and D were measured in various pH media(water,0.01 mol/L hydrochloric acid,pH 4.5 acetate buffer,and pH 6.8 PBS).The results showed that there were significant differences in the apparent dissolution rate,apparent solubility,and intrinsic dissolution rate between the two crystal forms in pH 6.8 PBS.According to the test results,both crystal forms of 1 showed the high solubility.The results of the parallel artificial membrane permeation test showed that the effective permeability coefficient of 1 was 8×10^(–5)-9×10^(–5) cm/s,indicating they had high permeability.Although both crystal forms in this study could be classified to BCS classⅠdrugs,there were certain differences in solubility and dissolution rates,crystal structure,and melting point,which should be given some references for screening the crystal forms of drug substance in formulation development.

关 键 词：酒石酸唑吡坦 多晶型 表观溶解速率 固有溶出速率 渗透性 

分 类 号：R971.3[医药卫生—药品] O645.12[医药卫生—药学] O742.4[理学—物理化学]