载药量和成膜材料HPMC相对分子质量对盐酸氟桂利嗪纳米晶口溶膜关键质量属性的影响  

Effects of Drug Loading and Relative Molecular Weight of Film Forming Material HPMC on Critical Quality Attributes of Flunarizine Hydrochloride Nanocrystalline Orodispersible Films

作　　者：刘国敏 翟豪 蔡挺 LIU Guomin;ZHAI Hao;CAI Ting(School of Pharmacy,China Pharmaceutical University,Nanjing 210009;School of Engineering,China Pharmaceutical University,Nanjing 211198;Engineering Research Center for Smart Pharmaceutical Manufacturing Technologies,China Pharmaceutical University,Nanjing 211198)

机构地区：[1]中国药科大学药学院,江苏南京210009 [2]中国药科大学工学院,江苏南京211198 [3]中国药科大学教育部智能制药关键技术工程研究中心,江苏南京211198

出　　处：《中国医药工业杂志》2024年第3期353-360,共8页Chinese Journal of Pharmaceuticals

摘　　要：盐酸氟桂利嗪(1)的低溶解度易导致口服生物利用度偏低。为提高1溶解度,该文采用反溶剂法制备了1纳米晶混悬液,再用流延浇铸法制成口溶膜,并考察了载药量和成膜材料HPMC的相对分子质量(M_(r):5×10^(4)~4×10^(5))对纳米晶口溶膜关键质量属性的影响。结果表明,载药量在低于40%时对1纳米晶口溶膜的再分散性无显著性影响;在受试范围内,HPMC M_r越大,1纳米晶口溶膜的再分散性越差。以HPMC E15、HPMC E50和HPMC E4M为膜材时:载药量在20%~30%范围内,1纳米晶在膜中分布均匀;当载药量高于40%时,1纳米晶在膜中可发生聚集。同时,纳米晶口溶膜的侵蚀和溶出性能具有较好的相关性:载药量和HPMC Mr越高,膜的侵蚀和溶出速率越慢。The low solubility of flunarizine hydrochloride(1)can lead to the low oral bioavailability.In order to increase the solubility of 1,1 nanocrystal suspension was prepared by the antisolvent crystallization method in this study.The orodispersible films containing 1 nanocrystals were then prepared by the solvent casting method.The effects of drug loading and relative molecular weight(M_(r):5×10^(4)-4×10^(5))of HPMC on the critical quality attributes of the orodispersible films were investigated.The results revealed that the redispersibility of the nanocrystalline orodispersible films was not significantly affected when the drug loading was lower than 40%.However,within the test ranges,the larger the Mr of HPMC,the worse the redispersibility of the 1 nanocrystalline orodispersible films.When the drug loading was in the range of 20%-30%,1 nanocrystal was evenly distributed in the films containing HPMC E15,HPMC E50,or HPMC E4M as the film forming material.However,when the drug loading was higher than 40%,1 nanocrystal tended to aggregate in the films.Furthermore,the results showed a good correlation between the erosion and dissolution performance of the films,where the higher the drug loading and Mr of HPMC resulted in the slower the erosion and dissolution rates of the film.

关 键 词：盐酸氟桂利嗪 纳米晶 口溶膜 载药量 相对分子质量 关键质量属性 

分 类 号：R944.9[医药卫生—药剂学]