Polymorphs of pridopidine hydrochloride

摘要

Pridopidine hydrochloride (Huntexil, NeuroSearch A/S, Ballerup, Denmark) is a dopaminergic stabilizer, currently in development for the treatment of motor symptoms associated with Huntington's disease. In this study, two polymorphic forms are characterized, forms I and II. The crystal structures of both polymorphs contain N ~+-H???Cl ~-???N ~+-H??? interactions, and the polymorphism can be viewed as alternative orientations (parallel or antiparallel) of comparable molecular columns while retaining the ???N ~+-H???Cl ~-???N ~+-H??? motif between columns. Forms I and II have melting points of 199 and 210 °C, respectively. Following melting of form I, a kinetically controlled crystallization to form II is observed. The polymorphs are enantiotropically related, form I being stable at ambient conditions and form II being stable above 127 °C. At around 180 °C, the differential scanning calorimetry thermogram of a mixture of forms I and II shows a solid-state transition from form I to form II, which is not observed for pure form I samples. Transformation of form II to form I below the transition temperature is solution-mediated. Because of the thermodynamic relation and the propensity for transformations, the safety, quality, and efficacy of pridopidine hydrochloride is not affected by the existence of form II.