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Communication Dans Un Congrès Année : 2022

Carbamazepine/Tartaric Acid Ordered and Disordered Cocrystalline Forms: When Stoichiometry and Synthesis Method Matter

Résumé

A deep investigation of the cocrystallization of the model pharmaceutical compound carbamazepine (CBZ) with DL-tartaric acid (DL-TA) and L-tartaric acid (L-TA) has been undertaken. Different synthesis techniques (liquid assisted grinding, solution evaporation and mechanical/solvent free conversion) and various stoichiometric ratios of parent components were tested. A structural, dynamical and thermodynamic information from complementarycharacterization techniques (X-ray diffraction, dielectric relaxation spectroscopy, differential scanning calorimetry and thermogravimetric analysis) combined with molecular dynamics simulations allow the comparison of the multicomponent systems obtained from the two coformers, and the evaluation of the impact of the synthesis methods and the stoichiometric composition. Interestingly, by liquid-assisted grinding of carbamazepine and DL-TA at a stoichiometric molar ratio of (1:1), a pure fully ordered cocrystal, CBZ:DL-TA (1:1) is obtained with high reproducibility. Oppositely, it is also shown that CBZ may form some isostructuralcrystal similar channel-like cocrystals with (partially) disordered TA coformer molecules (DL- or L-TA). By varying the molar ratios of the co-milled CBZ and L-TA parent compounds, with a catalytic amount of solvent (methanol), it is shown that a pure disordered cocrystal can be designed with a molar stoichiometry of (3:1) (100% conversion of parent compounds). The nature of the rotational dynamical disorder of the isostructural channel-like cocrystalline forms with L-TA coformer molecules have been particularly analyzed and how TA molecules may contribute for the stability of the CBZ-based channels. Rotational dynamics is interpreted asrotational jumps between preferred molecular orientations. It gives rise to a change of the molecular dipole moments orientations, which are detected by dielectric relaxation spectroscopy. Freezing out of the rotational molecular mobility is detected in the temperature range [173, 193] K concomitantly with the presence of a kink in the temperature evolution of the crystalline cell volume which is usually associated with the glass transition phenomenon. It reveals a remarkable link between the molecular mobility of the tartaric acid molecules and theoverall crystal anharmonicity. The present findings aim to demonstrate the interest of disordered channel-like cocrystals for investigation of dynamics in nanoconfinement environments.
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Dates et versions

hal-03969717 , version 1 (02-02-2023)

Identifiants

  • HAL Id : hal-03969717 , version 1

Citer

Natália T. Correia, Luisa-Viviane Roca Paixao, Frédéric Affouard. Carbamazepine/Tartaric Acid Ordered and Disordered Cocrystalline Forms: When Stoichiometry and Synthesis Method Matter. CGOM14: 14 th International Conference on Crystal Growth of Organic Materials, Sep 2022, Bruxelles, Belgium. ⟨hal-03969717⟩
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