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...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.展开更多
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
文摘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.
