混合溶剂改善他达拉非固体分散体物理稳定性的考察  

Investigation on Improving Physical Stability of Tadalafil Solid Dispersions by Cosolvent

作　　者：张晓婷 罗丹冬[1] 李庆国[2] 丘振文[1] ZHANG Xiaoting;LUO Dandong;LI Qingguo;QIU Zhenwen(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405;School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]广州中医药大学中药学院,广东广州510006

出　　处：《中国医药工业杂志》2020年第11期1418-1423,共6页Chinese Journal of Pharmaceuticals

摘　　要：为增加他达拉非固体分散体的物理稳定性,考察了共溶剂对制品中药物的存在状态和溶出度的影响。本试验通过喷雾干燥技术,以丙酮及其与3种共溶剂(即水、0.1%甲酸溶液和无水乙醇)的混合体系制备他达拉非固体分散体。采用动态光散射法测定载体聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)在不同溶剂体系中的粒径,以考察药物与载体间的相容性。继而采用傅里叶变换红外光谱、X射线粉末衍射、差示扫描量热法对不同混合溶剂体系制备的他达拉非固体分散体进行表征,并测定其在0.1%十二烷基硫酸钠溶液中的溶出行为。同时考察了不同固体分散体在(40±2)℃、相对湿度(75±5)%的环境中放置3个月的初步稳定性。结果表明,与纯丙酮相比,混合溶剂丙酮∶水(7∶3)提高了溶液中他达拉非和Soluplus的相容性,得到的相应固体分散体在受试制品中具有较优的溶出度和良好的稳定性。To improve the physical stability of tadalafil solid dispersions(SDs),the effect of cosolvent on the existing state and dissolution of tadalafil in SDs was investigated.The carrier,polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer(Soluplus),and drug were dissolved in acetone or different mixed solvents consisted of acetone and three cosolvents(water,0.1%formic acid solution and absolute ethanol),then these systems were spray dried to obtain tadalafil SDs.The dynamic light scattering method was used to analyze the average particle size of Soluplus for evaluating the compatibility between tadalafil and Soluplus in different solvent systems.The prepared SDs were characterized by Fourier-transform infrared spectroscopy,X-ray powder diffraction and differential scanning calorimetry,and their dissolution profiles in 0.1%sodium dodecyl sulfate solution were also investigated.Furtherly,the preliminary stabilities of different SDs stored at(40±2)℃and(75±5)%of relative humidity for 3 months were tested to evaluate the changes in physical properties of the SDs prepared with different mixed solvent systems.The results showed that the mixed solvents consisted of acetone and water in the ratio of 7∶3 improved the compatibility between tadalafil and Soluplus compared with pure acetone,and the corresponding SDs had a superior dissolution rate and good stability among the prepared SDs.

关 键 词：混合溶剂 他达拉非 喷雾干燥 固体分散体 稳定性 

分 类 号：R944.9[医药卫生—药剂学]