In
this work, the solid–liquid equilibrium for levetiracetam
in 10 neat solvents (methanol, ethanol, n-propanol,
isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, toluene,
and cyclohexane) and binary liquid mixtures (ethanol + ethyl acetate)
was measured by using a static gravimetric method at temperatures T = 283.15–323.15 K under pressure of 101.2 kPa.
In general, the equilibrium solubility was highest in methanol and
lowest in cyclohexane. The modified Apelblat equation, λh equation, Wilson model, and NRTL model were used to correlate the
solubility data in monosolvents; and the Jouyban–Acree model,
van’t Hoff–Jouyban–Acree model, and Apelblat–Jouyban–Acree
model were used to correlate the experiment data in the binary solvent
mixtures. Compared with the results of the above models, the calculated
solubility provided good results with the experimental data. Consequently,
for the monosolvents, the values of root-mean-square deviation and
relative average deviation were not exceeding 9.91 × 10–4 and 2.50%, respectively; and for the binary solvent mixtures, 2.75
× 10–4 and 0.80%. Furthermore, the thermodynamic
properties of levetiracetam in monosolvents were calculated. From
the analysis results, the dissolution process of levetiracetam was
an endothermic, spontaneous, and entropy driven process. It is crucially
important to understand the solubility and thermodynamic properties
of levetiracetam in drug development. In particular, purification,
recrystallization, and formulation development of levetiracetam in
industry were effected by its solubility values.