J.Th.H. van
Eupen, R. Westheim, M.A.
Deij, H. Meekes, P. Bennema, E. Vlieg,
The solubility
behaviour and
thermodynamic relations of the three forms of venlafaxine free base.
Int. Journal of Pharm. 368 (2009)
146-153
Abstract
The polymorphic and solubility behaviour
of the active pharmaceutical ingredient Venlafaxine free base, which is
used as an antidepressant, is studied. Using differential scanning
calorimetry and slurry experiments, an enantiotropic relation between
the three forms was found. Transition temperatures were determined
using solubility data and compared with calculated transition
temperatures based on the melting enthalpies and temperatures of the
different forms. The solubility of Venlafaxine in heptane, toluene and
methanol shows a large deviation from ideal behaviour. The deviations
are to a large extent determined by the temperature dependence of the
difference in fusion enthalpy of the undercooled melt and the solid.