title: Development of a liquid formulation of poorly water-soluble isosteviol sodium using the co-solvent technology.
abstract: 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.
authors.affiliation: 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.
authors.forename: Wenshi
authors.initials: W
authors.lastname: Lai
authors.affiliation: 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.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Chengjuan
authors.initials: C
authors.lastname: Zou
authors.affiliation: 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.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Huiting
authors.initials: H
authors.lastname: Sun
authors.affiliation: a School of Bioscience and Bioengineering, South China University of Technology , Guangzhou , China.|c Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology , Guangzhou , China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002460:Cell Line; D045786:Diterpenes, Kaurane / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry* / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D014677:Pharmaceutical Vehicles / Q000737:chemistry* / Q000633:toxicity; D019946:Propylene Glycol / Q000737:chemistry* / Q000633:toxicity; D017208:Rats, Wistar; D012995:Solubility; D012997:Solvents / Q000737:chemistry / Q000633:toxicity; D014867:Water / Q000737:chemistry
chemical_list: D045786:Diterpenes, Kaurane; D014677:Pharmaceutical Vehicles; D012997:Solvents; D014867:Water; C515747:isosteviol; D000431:Ethanol; D019946:Propylene Glycol
keywords: Isosteviol sodium; co-solvent; intravenous injection; liquid formulation; poorly water soluble