Solvent screening and crystal habit of metformin hydrochloride

•A multi-well set-up was used as a rapid tool to investigate Metformin Hydrochloride crystallization.•Solubility in 13 varied solvents was measured.•Different crystal habit appeared in five of six good solvents selected after the screening.•All crystals were characterized by MO, SEM, DSC and DRX.•Solubility data analysis and toxicity of solvents permits us to minimize the number of crystallization medium.

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.HCl). Starting with 13 solvents covering a wide variety of polarity and proticity, we found 63 crystallization medium for MET.HCl 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.HCl, 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.HCl. Finally, the enthalpy of fusion and the melting temperature of MET.HCl were determined by DSC and confirmed the X-ray powder diffraction results.