화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.131, No.13, 4554-4554, 2009
Polymer-Induced Heteronucleation of Tolfenamic Acid: Structural Investigation of a Pentamorph
The nonsteroidal anti-inflammatory drug (NSAID) tolfenamic acid (TA), previously thought to be dimorphic, is demonstrated to have at least five polymorphs. The new forms were uncovered through the emerging screening technique of polymer-induced heteronucleation (PIHn). The presence of conformational changes among forms, whole molecule disorder, space group diversity, and varying number of molecules in the asymmetric unit occurring within a very narrow free energy window (similar to 0.3 kcal/mol) make the solid-state chemistry of this molecule uniquely complex among pharmaceuticals. These aspects make it a particularly suitable benchmark compound for crystal structure prediction methods.