Solvent screening and crystal habit of metformin hydrochloride

Ibtissem Benmessaoud , Ouahiba Koutchoukali , Mohamed Bouhelassa (1) , Abderrahim Nouar , Stéphane A Veesler (2)

1 Université Salah Boubnider Constantine 3
2 CINaM - Centre Interdisciplinaire de Nanoscience de Marseille

A multi-well setup with video-microscopy was used to study the influence of solvent on solubility, nucleation, and crystallization of an Active Pharmaceutical Ingredient (API): metformin hydrochloride (MET.HCI). Starting with 13 solvents covering a wide variety of polarity and proticity, we found 63 crystallization medium for MET.HCI solid generation: good solvents, good co-solvents and anti-solvent systems. For toxicological reasons, we limited the number of crystallization medium to 18: 3 good solvents (class 3), 3 good co-solvent systems and 12 anti-solvent systems. In order to study the influence of crystallization medium on nucleation temperature, crystal habit and polymorphism of MET.HCI, crystallization was studied by a cooling temperature method. Different crystal habits were observed by optical and scanning electron microscopies, and solid phase were characterized by X-ray powder diffraction, indicating that all the crystals correspond to the thermodynamic stable polymorphic form A of MET.HCI. Finally, the enthalpy of fusion and the melting temperature of MET.HCI were determined by DSC and confirmed the X-ray powder diffraction results. (C) 2016 Elsevier B.V. All rights reserved.

Domaines: Physique [physics]

Ibtissem Benmessaoud, Ouahiba Koutchoukali, Mohamed Bouhelassa, Abderrahim Nouar, Stéphane A Veesler. Solvent screening and crystal habit of metformin hydrochloride. Journal of Crystal Growth, 2016, 451, pp.42-51. ⟨10.1016/j.jcrysgro.2016.07.001⟩. ⟨hal-01454994⟩