Thermodynamics Research Center, ThermoML : Journal of Chemical Thermodynamics

Improving the solubility of temozolomide by cosolvent and its correlation with the Jouyban-Acree and CNIBS/R-K models

Li, R.[Rongrong], Yin, X.[Xianfang], Zhang, J.[Jieyu], Tang, T.[Tian], Fang, X.[Xuchong], Zhang, L.[Lubing], Xu, W.[Wenjie], Zhao, J.[Jia], Han, D.[Deman]
J. Chem. Thermodyn. 2019, 139, 105875
ABSTRACT
In recent years, the number of insoluble drug candidates has increased, with almost 70% of new drug candidates showing poor solubility. Cosolvent was used in this work to improve the solubility of poorly soluble temozolomide. The solubility data of temozolomide in four mixed solvents including (ethyl acetate + methanol), (ethyl acetate + ethanol), (ethyl acetate + n-propanol) and (ethyl acetate + isopropanol) at temperatures from 273.15 to 318.15 K were determined and evaluated by Jouyban-Acree model and CNIBS/R-K model. In mixtures of (ethyl acetate + methanol) and (ethyl acetate + ethanol) and at a certain temperature, the values increase with increasing cosolvent (ethyl acetate) mass fraction w to a maximum at w = 0.6 and then decrease, while it increases to a maximum at w = 0.8 in (ethyl acetate + n-propanol) and (ethyl acetate + isopropanol). Particularly, the effect of cosolvent on the dissolution process of temozolomide is an important aspect of its recrystallization and purification. All the values of RMSD and RAD are no more than 3.77 10 2 and 2.2 10 5, respectively. It shows that both thermodynamic models can be used to correlate solubility data of objective compound. Moreover, the results of apparent thermodynamic analysis indicate that the dissolution is a favorable, endothermic and entropy driven process.
Compounds
# Formula Name
1 C6H6N6O2 Temozolomide
2 CH4O methanol
3 C2H6O ethanol
4 C3H8O propan-2-ol
5 C3H8O propan-1-ol
6 C4H8O2 ethyl acetate
Datasets
The table above is generated from the ThermoML associated json file (link above). POMD and RXND refer to PureOrMixture and Reaction Datasets. The compound numbers are included in properties, variables, and phases, if specificied; the numbers refer to the table of compounds on the left.
Type Compound-# Property Variable Constraint Phase Method #Points
  • POMD
  • 1
  • 6
  • 2
  • Mole fraction - 1 ; Liquid
  • Solvent: Mass fraction - 6; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 60
  • POMD
  • 1
  • 6
  • 3
  • Mole fraction - 1 ; Liquid
  • Solvent: Mass fraction - 6; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 60
  • POMD
  • 1
  • 6
  • 4
  • Mole fraction - 1 ; Liquid
  • Solvent: Mass fraction - 6; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 60
  • POMD
  • 1
  • 6
  • 5
  • Mole fraction - 1 ; Liquid
  • Solvent: Mass fraction - 6; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 60
  • POMD
  • 1
  • 2
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 10
  • POMD
  • 1
  • 6
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 10
  • POMD
  • 1
  • 3
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 10
  • POMD
  • 1
  • 4
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 10
  • POMD
  • 1
  • 5
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 10