文献类型：期刊文献

英文题名：Novel Salts of the Atypical Antipsychotic Drug Lurasidone with Improved Solubility and Bioavailability

作者：Guo, Chunyang[1];Wang, Yuan[1];Xie, Junyi[1];Zhu, Bin[1];Qi, Ming-Hui[1];Hong, Minghuang[1];Ren, Guo-Bin[1,2]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Lab Pharmaceut Crystal Engn & Technol, Minist Educ, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2023

卷号：23

期号：1

起止页码：326

外文期刊名：CRYSTAL GROWTH & DESIGN

收录：;EI(收录号：20225213315126);WOS:【SCI-EXPANDED(收录号:WOS:000904091800001)】；

基金：ACKNOWLEDGMENTS The authors acknowledge the support from the National Natural Science Foundation of China (Grant Nos. 22078094, 21776073, and 22108073) and the Natural Science Founda- tion of Shanghai (Grant No. 20ZR1413600) .

语种：英文

外文关键词：Biochemistry - Drug delivery - Single crystals - Solubility - Thermoanalysis - X ray diffraction

摘要：Lurasidone is an atypical antipsychotic drug for treating schizophrenia and bipolar disorder. The commercial form of lurasidone hydrochloride performs poor bioavailability and significant food effect owing to its poor water solubility. In this study, three novel salts of lurasidone, namely, lurasidone- ketoglutaric acid (LUD-KTA), lurasidone-trans-aconitic acid (LUD-TAA), and lurasidone-maleic acid (LUD-MA-H2O), were obtained and characterized by powder X-ray diffraction and thermal analyses. The molecular components and structures were confirmed by single-crystal X-ray diffraction. The results of the stability experiment showed that LUD-KTA and LUD-TAA exhibited satisfying physical stabilities. Based on in vitro powder dissolution experiments, the new salts achieved remarkably higher solubility than LUD-HCl. In addition, in vivo studies also showed that LUD-KTA and LUD-TAA provided superior bioavailability.