کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1789488 | 1524378 | 2016 | 10 صفحه PDF | دانلود رایگان |
• 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.
Journal: Journal of Crystal Growth - Volume 451, 1 October 2016, Pages 42–51