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.