Thermodynamics Research Center / ThermoML | Journal of Chemical Thermodynamics

Solubility parameter of lenalidomide for predicting the type of solubility profile and application of thermodynamic model

Yang, Z.[Zehui], Shao, D.[Danfeng], Zhou, G.[Guoquan]
J. Chem. Thermodyn. 2019, 132, 268-275
ABSTRACT
The dissolving capacity of lenalidomide in pure and mixed solvents is limited. The purpose of this work is to enhance the solubility and study the solubility parameter of pure and mixtures (d1) to characterize different types of solubility profiles. The solubility of lenalidomide in acetonitrile (MeCN), methanol (MT), ethanol (EA), ethyl acetate (EAC) and isopropanol (IPA) was experimentally determined at T = 293.15 333.15 K. Its solubility in binary mixtures of EA and EAC was also investigated. The polarity of lenalidomide is related to the tendency of the solubility data against the solubility parameter d1 of pure and binary solvent mixtures. Consequently, the method of linear solvation energy relationships introduced by Kamlet, Abboud and Taft (KAT-LSER) was applied to analyze the effect of the solute-solvent intermolecular interactions on the solubility in pure solvents. In order to estimate maximum solubility in a specific co-solvent ratio, we also attempt to calculate the Hansen solubility parameter (HSP) of lenalidomide and to compare it with HSP of solvent mixture. Based on the experimental solubility data, two thermodynamic models including modified Apelblat equation and Jouyban-Acree model were then assessed. Meanwhile, a modification of the extended Hildebrand solubility approach (EHSA) including the Hildebrand solubility parameter (d1) and the acidic and basic partial solubility parameters (d1a and d1b) of the solvent mixtures was used to simulate lenalidomide solubility in pure and binary mixture compositions.
Compounds
# Formula Name
1 C13H13N3O3 lenalidomide
2 C2H6O ethanol
3 CH4O methanol
4 C3H8O propan-2-ol
5 C2H3N acetonitrile
6 C4H8O2 ethyl acetate
7 C7H6O2 benzoic acid
8 C7H8 toluene
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
  • 7
  • 8
  • Mole fraction - 7 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 7
  • Chromatography
  • 4
  • POMD
  • 1
  • 3
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 9
  • POMD
  • 1
  • 2
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 9
  • POMD
  • 1
  • 4
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 9
  • POMD
  • 1
  • 5
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 9
  • POMD
  • 1
  • 6
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 9
  • POMD
  • 1
  • 6
  • 2
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Solvent: Mass fraction - 6; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 1
  • Chromatography
  • 90