ABSTRACT

The solubility of candesartan cilexetil (Form I) was measured by a gravimetric method in aqueous solvent mixtures (ethanol-water, acetonitrile-water and acetone-water), and the calculated values by (NIBS)/Redlich-Kister equation agreed well with the experimental data. The relationship between solubility of candesartan cilexetil (Form I) and molar fraction of organic solvents (ethanol, acetonitrile and acetone) shown unimodal curves, and this phenomenon can be explained by delta-H_sol - delta-G_sol compensation theory. For ethanol-water and acetonitrile-water mixture, the plot of delta-H_sol - delta-G_sol compensation was nonlinear with positive and negative slopes, indicating that the increases of solubility were controlled by two different mechanisms (entropy and enthalpy). However, for acetone-water mixture, the plot of delta-H_sol - delta-G_sol compensation was a linear curve, indicating that enthalpy is the dominant mechanism to control the solubility enhancement. These results can also be used to explain that acetone molecule played an important role in increasing the solute-solvent interactions of the candesartan cilexetil (Form I).

Compounds

#	Formula	Name
1	C33H34N6O6	1-(((cyclohexyloxy)carbonyl)oxy)ethyl 1-((2-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate
2	H2O	water
3	C2H6O	ethanol
4	C2H3N	acetonitrile
5	C3H6O	acetone

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	Normal melting temperature, K ; Crystal			Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	1	Molar enthalpy of transition or fusion, kJ/mol ; Crystal			Crystal Liquid Air at 1 atmosphere	DSC	1
POMD	3 2 1	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 3; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric method	55
POMD	4 2 1	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 4; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric method	50
POMD	5 2 1	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 5; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric method	55

Thermodynamics Research Center / ThermoML | Fluid Phase Equilibria

Thermodynamic analysis and correlation of solubility of candesartan cilexetil in aqueous solvent mixtures

Cui, P.[Penglei], Yin, Q.[Qiuxiang], Gong, J.[Junbo], Wang, Y.[Yongli], Hao, H.[Hongxun], Xie, C.[Chuang], Bao, Y.[Ying], Zhang, M.[Meijing], Hou, B.[Baohong], Wang, J.[Jingkang]

ABSTRACT