Polymorphs of Pridopidine Hydrochloride

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.