Lai Wenshi, Kang Qiuhong, Zou Chengjuan, Li Qingrui, Sun Huiting, Tan Wen
a School of Bioscience and Bioengineering, South China University of Technology , Guangzhou , China.
b Pre-incubator for Innovative Drugs and Medicine, South China University of Technology , Guangzhou , China.
Pharm Dev Technol. 2017 Mar;22(2):275-282. doi: 10.1080/10837450.2016.1226900. Epub 2016 Sep 21.
An intravenously injectable liquid formulation of the poorly water-soluble isosteviol sodium (ISVNa) that has a great clinical potential for cardiovascular diseases was developed using the co-solvent technology. The pH and composition of the co-solvent were optimized to obtain a stable liquid formulation (termed as STVNa) based on saline at pH 10.0 containing 25% (v/v) of ethanol and 20% (v/v) of propylene glycol. STVNa was physicochemically stable upon storage for more than 3 months under various conditions. In vitro studies showed that STVNa did not induce hemolytic effects up to 9.1% (v/v) after 3 h of incubation and it was cytocompatible up to 50 μg/mL in H2C9 cells. Furthermore, STVNa showed acceptable safety and pharmacokinetic parameters comparable with those of ISVNa in saline (dissolved at 60 °C) upon i.v. injection in Wistar rats. Overall, the results demonstrated that STVNa is a promising formulation of ISVNa for clinical translation.
采用共溶剂技术开发了一种水溶性差的异甜菊醇钠（ISVNa）静脉注射液体制剂，该制剂在心血管疾病方面具有巨大的临床潜力。优化共溶剂的pH值和组成，以获得基于pH 10.0的生理盐水的稳定液体制剂（称为STVNa），其中含有25%（v/v）的乙醇和20%（v/v）的丙二醇。STVNa在各种条件下储存3个月以上时，理化性质稳定。体外研究表明，STVNa在孵育3小时后，浓度高达9.1%（v/v）时不会引起溶血作用，并且在H2C9细胞中，浓度高达50μg/mL时具有细胞相容性。此外，在Wistar大鼠静脉注射后，STVNa显示出与ISVNa在生理盐水中（60°C溶解）相当的可接受的安全性和药代动力学参数。总体而言，结果表明STVNa是一种有前景的ISVNa临床转化制剂。
