Detection and characterization of polymorphic modifications of the anxiolytic drug ABECARNIL

Abstract

Polymorphism is of special interest in pharmaceutical research since the stability and the biological activity of a drug substance are influenced by its solid state form. For the anxiolytic β-carboline compound ABECARNIL (isopropyl 6-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylate, C 24H 24N 2O 4) three different modification have been observed. Single crystal X-ray structure analyses and a variety of physicochemical methods as well as energy minimizations have been carried out in order to characterize the three solid state forms and to find at least one method capable of differentiating between the polymorphic forms. Due to nearly identical conformations and very similar packings of the molecules within their crystal lattices, polymorphs A and B show a pronounced resemblance in most physicochemical properties. Nevertheless, both forms can be distinguished by X-ray power diffraction and differential scanning calorimetry. In the crystal, molecules belonging to polymorph C show altered conformation and packing characteristics compared to forms A and B. Polymorph C can therefore be distinguished from the other solid state form by means of X-ray powder diffraction, differential scanning calorimetry and by IR spectroscopy. The relative energy of C in the crystalline environment is significantly lower than for the other two modifications.