Objectives
To prepare new crystalline forms of the antidepressant o‐desmethylvenlafaxine salt as potential new commercial forms and evaluate their physicochemical properties, in particular the dissolution rate.
Methods
A new hydrogen oxalate salt of o‐desmethylvenlafaxine hydrogen oxalate (ODV‐OX) was synthesized, and a polymorph screening was performed using different solvents and crystallization conditions. Crystalline forms were characterized by a combination of solid‐state techniques: X‐ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, FT‐IR spectroscopy and single crystal X‐ray diffraction. The stability of all crystalline phases was tested under International Conference on Harmonisation (ICH) conditions (40°C and 75% Relative Humidity (RH)) for 1 week. Dissolution tests were performed on the hydrogen oxalate salt ODV‐OX Form 1 and compared with dissolution test on the commercial form of the succinate salt of o‐desmethylvenlafaxine.
Key findings
Five crystalline forms of ODV‐OX were isolated, namely three hydrated forms (Form 1, Form 2, Form 3) and two anhydrous forms (Form 4 and Form 5).
Conclusions
Comparative solubility tests on ODV‐OX Form 1 and o‐desmethylvenlafaxine succinate evidenced a significant increase in solubility for the hydrogen oxalate salt (142 g/l) with respect to the succinate salt (70 g/l).