The solubility behaviour and thermodynamic relations of the three forms of Venlafaxine free base.
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.
van Eupen
J Th H
JT
IMM, Solid State Chemistry, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Westheim
R
R
Deij
M A
MA
Meekes
H
H
Bennema
P
P
Vlieg
E
E
D000928:Antidepressive Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D003511:Cyclohexanols / Q000737:chemistry*; D004355:Drug Stability; D015394:Molecular Structure; D044367:Phase Transition; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D044366:Transition Temperature; D000069470:Venlafaxine Hydrochloride; D014961:X-Ray Diffraction
D000928:Antidepressive Agents; D003511:Cyclohexanols; D012997:Solvents; D000069470:Venlafaxine Hydrochloride