Solubility of Agomelatine Crystal Form I and Form II in Pure Solvents and (Isopropanol + Water) Mixtures

Solubility of agomelatine crystal form II in five pure solvents and (isopropanol + water) binary mixtures was measured from 273.15 K to 313.15 K. The temperature and molar fraction of isopropanol were kept lower range to ensure that no polymorphic transformation would be observed during measuring solubility of form I, which would be determined by XRPD. Thus, solubility of form I was determined under temperature range (from 273.15 K to 293.15 K) in the same binary mixtures with lower molar fraction of isopropanol. All of experimental solubility were correlated by modified Apelblat equation. In addition, the change of molar enthalpy of agomelatine during dissolution was calculated by the empirical parameters of modified Apelblat equation. Furthermore, compared with solubility of form II in the same solvent system, solubility of form I is approximately twice higher than solubility of form II in isopropanol (xB = 0.0494 and 0.0642) + water binary mixtures under the temperature range (from 273.15 K to 293.15 K).