title: Crystal forms of the hydrogen oxalate salt of o-desmethylvenlafaxine.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
authors: PolyCrystalLine s.r.l., Bologna, Italy.
authors: Elena
authors: E
authors: Dichiarante
authors: PolyCrystalLine s.r.l., Bologna, Italy.
authors: Marco
authors: M
authors: Curzi
authors: PolyCrystalLine s.r.l., Bologna, Italy.
authors: Stefano L
authors: SL
authors: Giaffreda
authors: Dipartimento di Chimica G. Ciamician, University of Bologna, Bologna, Italy.
authors: Fabrizia
authors: F
authors: Grepioni
authors: Dipartimento di Chimica G. Ciamician, University of Bologna, Bologna, Italy.
authors: Lucia
authors: L
authors: Maini
authors: Dipartimento di Chimica G. Ciamician, University of Bologna, Bologna, Italy.
authors: Dario
authors: D
authors: Braga
mesh_terms: D000928:Antidepressive Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D000069468:Desvenlafaxine Succinate / Q000737:chemistry*; D004304:Dosage Forms; D004355:Drug Stability; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D015394:Molecular Structure; D010070:Oxalates / Q000737:chemistry*; D011208:Powders; D012492:Salts / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013386:Succinates / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D013818:Thermogravimetry
chemical_list: D000928:Antidepressive Agents; D004304:Dosage Forms; D010070:Oxalates; D011208:Powders; D012492:Salts; D012997:Solvents; D013386:Succinates; D006859:Hydrogen; D000069468:Desvenlafaxine Succinate
keywords: crystal form; dissolution test; hydrate; o-desmethylvenlafaxine; solid-state characterization