Stable Polymorph of Venlafaxine Hydrochloride by Solid-to-Solid Phase Transition at High Temperature

A novel polymorph of the antidepressant drug venlafaxine hydrochloride (VenHCl) was visualized in thermal microscopy and identified by variable-temperature powder X-ray diffraction at 180−190 °C. Its single-crystal X-ray structure was solved and refined satisfactorily in P21/n space group (form 6, Z‘ = 2, T = 100 K, R 1 = 0.1073). The powder X-ray diffraction pattern and melting point of form 6 are significantly different from the known polymorphs 1−5. Form 6 has a higher melting point and is more stable than marketed drug forms 1 and 2.