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Solid-State Overview of R-Baclofen: Relative Stability of Forms A, B and C and Characterization of a New
Nicolas Couvrat1, Morgane Sanselme1, Manon Poupard1
1Normandie Univ, Univ Rouen Normandie, SMS-EA3233, Place Emile Blondel, 76130 Mont-Saint-Aignan, France.
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 A < C < B at 25 °C (A is the most stable form), whereas above 180 °C it would likely be: C < A < B (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.
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