Polymorphism
and migratory chiral resolution of the free base of venlafaxine. a
remarkable topotactical solid state transition from a racemate to a
racemic conglomerate
Author(s): van Eupen JTH , Elffrink
WWJ , Keltjens R , Bennema P , de Gelder R, Smits JMM , van Eck ERH ,
Kentgens APM, Deij MA , Meekes H , Vlieg E
Cryst. Growth & Des. 8 no. 1
(2008) 71-79
Abstract:
The unique behavior of the active
pharmaceutical ingredient Venlafaxine free base, used as an
antidepressant, with respect to polymorphism and chiral resolution is
reported. Using several complementary techniques, three crystal
structures of Venlafaxine were identified and isolated. All three
structures are composed of virtually identical enantiomeric pure layers
with different stacking modes. In the crystal structure with the
highest melting point, the enantiomeric separation is complete, leading
to a racemic conglomerate. The conglomerate can be grown from solution
or via a solid-solid phase transition of the lowest melting racemic
compound. Remarkably, the crystal shape is conserved during the
transition. The corresponding chiral resolution is achieved via a local
melting process, allowing for a long-range migration of the molecules
between layers.