1. Solid-State Overview of R-Baclofen: Relative Stability of Forms A, B and C and Characterization of a New Heterosolvate
- Author
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Morgane Sanselme, Jean-Marie Schneider, Simon H. Drouin, Gérard Coquerel, Nicolas Couvrat, Manon Poupard, Céline Bensakoun, Sciences et Méthodes Séparatives (SMS), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)
- Subjects
Baclofen ,Materials science ,Solid-state ,Pharmaceutical Science ,02 engineering and technology ,Crystal structure ,030226 pharmacology & pharmacy ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,X-Ray Diffraction ,law ,(R)-Baclofen ,Crystallization ,ComputingMilieux_MISCELLANEOUS ,Calorimetry, Differential Scanning ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,Relative stability ,Characterization (materials science) ,Crystallography ,Enantiopure drug ,0210 nano-technology ,Powder Diffraction ,Powder diffraction - Abstract
A new polymorphic form (Form C) of enantiopure Baclofen was isolated and characterized. Crystal structures of R-Baclofen Form A and Form C were resolved from powder diffraction data, and cell parameters by profile matching for Form B. The relative stability of these three forms is proposed based on structural data, thermal analyses and solvent-mediated conversions. The experiments highlight the stability order ACB at 25 °C (A is the most stable form), whereas above 180 °C it would likely be: CAB (C being the stable modification). Moreover, a new heterosolvate of the molecule is observed in N,N-DMF/water mixture. This heterosolvate offers a new pathway to isolate pure R-Baclofen Form B provided the lactam impurity does not exceed 3%. Upon mechanical stress Form B tends to evolve to Form C.
- Published
- 2021
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