Using Dissolution and Pharmacokinetics Studies of Crystal Form to Optimize the Original Iloperidone

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• 作者：Tingting Zhang ; Yan Yang ; Haitao Wang ; Fuxing Sun ; Xiaojun Zhao ; Jiangtiao Jia ; Jingrui Liu ; Wei Guo ; Xiaoqiang Cui ; Jingkai Gu ; Guangshan Zhu
• 刊名：Crystal Growth & Design
• 出版年：2013
• 出版时间：December 4, 2013
• 年：2013
• 卷：13
• 期：12
• 页码：5261-5266
• 全文大小：357K
• 年卷期：v.13,no.12(December 4, 2013)
• ISSN：1528-7505

文摘

The crystal engineering strategy was used to facilitate the supramolecular synthesis of a new crystalline phase of iloperidone, an atypical psychotropic drug with known problems related to poor dissolution and absorption profile. The novel crystal forms Jilin University China-Cocrystal-1 (JUC-C1), Jilin University China-Cocrystal-2 (JUC-C2), and Jilin University China-Cocrystal-3 (JUC-C3) of iloperidone with 3-hydroxybenzoic acid (3-HBA), 2,3-dihydroxybenzoic acid (2,3-DHBA), and 3,5-dihydroxybenzoic acid (3,5-DHBA) were obtained using the reaction crystallization method (RCM). The dissolution and pharmacokinetics studies were performed to exploit this atypical psychotropic drug. In the dissolution experiment, JUC-C1, JUC-C2, and JUC-C3 (JUC-C1鈥?) showed a much faster dissolution rate than the original active pharmaceutical ingredient (API) in simulated gastric fluid media (pH = 1.2). Furthermore, pharmacokinetic behavior of JUC-C1鈥? and API was investigated to evaluate the effectiveness of this strategy for enhancing the oral absorption of iloperidone. The in vitro and in vivo studies revealed that JUC-C2 possessed an excellent dissolution behavior and improved pharmacokinetic profile.