Abstract
The effects of seven kinds of impurities on the solvent-mediated transformation of crystal polymorphs of a drug substance AE1-923 were investigated. AE1-923 was developed for an indication of pollakiuria and pain. It has three polymorphs, namely the unstable A-form, the metastable B-form and the stable C-form. The impurities tested were the starting compounds, the reaction reagents and the intermediates in the synthesis of AE1-923. One of the impurities, an intermediate AE1-923ME (methylester of AE1-923), inhibited the solvent-mediated polymorph transformation of the B-form to the C-form, although the transformation of the A-form to the B-form was not inhibited. The other impurities had no effect on the two steps of polymorph transformation. The inhibitory effect of AE1-923ME that was evaluated by the overall transformation rate constant kc exponentially increased with an increase in the concentration of AE1-923ME. AE1-923ME of 0.5 wt% completely suppressed the nucleation of the stable C-form crystals. However, crystal growth of the C-form was not inhibited.
