A thorough analysis of the effect of surfactant/s on the solubility and pharmacokinetics of (S)-zaltoprofen

作     者：Cuong Viet Pham Jong-Suep Baek Jong-Hun Park Sang-Hun Jung Jong-Seong Kang Cheong-Weon Cho 

作者机构：College of Pharmacy and Institute of Drug Research and DevelopmentChungnam National UniversityDaejeon 34134Republic of Korea Department of HerbologyCollege of Korean MedicineDongguk UniversityGyeongju 38066Republic of Korea 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2019年第14卷第4期

页      面：435-444页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the Basic Science Research Program (2016R1A2B4011294) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education  Science and Technology 

主　　题：(S)-zaltoprofen Solubility Bioavailability D-alpha tocopheryl polyethylene glycol 1000 succinate 2-hydroxypropyl-β-cyclodextrin 

摘      要：Until now, there are no publications about the preformulation studies on(S)-zaltoprofen((S)-ZPF). Hence, we first investigated the solubility of(S)-ZPF, screened solubilizers and performed the pharmacokinetic study of(S)-ZPF in the presence of the solubilizers. The measurement of the solubility of(S)-ZPF in 26 different solvents was carried out, including d-alpha tocopheryl polyethylene glycol 1000 succinate(TPGS), 2-hydroxypropyl-β-cyclodextrin(HPCD), and mixtures of individual solvent. The plasma concentration of(S)-ZPF and the amount of(S)-ZPF retained in stomach were determined after oral(35.0 mg/kg) and intravenous(5.0 mg/kg) administration. The solubility of(S)-ZPF showed an increase of 484-fold in TPGS compared to its aqueous solubility. There was a significant increase of AUC 0-24 h for pure(S)-ZPF in the TPGS group(813.59 ± 64.17 μg h/ml) in comparison with AUC 0-24 h in the HPCD group(595.57 ± 71.76 μg h/ml) and water group(465.57 ± 90.89 μg h/ml). In addition, the T max of(S)-ZPF in the TPGS group was 2 h, much faster than that in the HPCD or water groups(5.50 or 5.67 h, respectively). This suggested that TPGS played a significant role in the increase of solubility and bioavailability of(S)-ZPF.