From photochemical and non-photochemical nucleation induced by LASER to experimental and theoretical interaction energy determination: Carbamazepine III a complete study

Anne Spasojevic - de Biré (1) , Aziza Ikni (1) , Nouha El Hassan (1) , Bertrand Clair (1) , Philippe Scouflaire (2) , Jean-Michel Gillet (1) , Nour-Eddine Ghermani (1, 3)

1 SPMS - Laboratoire Structures, Propriétés et Modélisation des solides
2 EM2C - Laboratoire d'Énergétique Moléculaire et Macroscopique, Combustion
3 IGPS - Institut Galien Paris-Sud

This paper deals with the nucleation of the carbamazepine (CBZ) molecule by using the Non Photochemical Laser Induced Nucleation (NPLIN). This method is recently demonstrated by Garetz (1) in the crystallization of Glycine (2), urea (3), and L-Histidine (4). This paper focuses on the CBZ molecule crystallisation. It was observed that on being exposed to the pulsed nanosecond laser (Q-switched Nd: YAG) with wavelength of 532 nm, the CBZ solutions yield an orange coloration. The hypothesis behind the orange coloration is a photochemical reaction that produces iminostilbene from the CBZ. This reaction occurs by breaking the N-CONH2 bond, the most fragile bond of the molecule and adding hydrogen to the N atom from the surrounding water molecule, present as the solvent or in the moisture. This paper is aimed to verify experimentally the hypothesis. We have imposed proper experimental conditions in order to avert the photochemical reaction resulting in orange coloration and to produce the crystal of CBZ from its solution at the metastable state by NPLIN. The influence of the solvents in the occurrence of the photochemical reaction was also studied in this experiment. Indeed, we used methanol which is a polar protic solvent and and Acetonitrile which is a polar aprotic solvent. The effect of polarization of laser beam on the crystal morphology and impact of energy on the crystallization was also studied by using both the linearly and circularly polarized light at different values of energy. We have for the first time shown that it is possible to obtain carbamazepine crystals using the NPLIN technique, avoiding any photochemical reaction. Moreover, we have obtained in a few days, under stable conditions, large crystals (of type III) high quality (fig 1). The experimental electron and electrostatic properties of carbamazepine drug molecule (form III) were determined from accurate high resolution X-ray diffraction data collected at 100 K. The results are compared to quantum

Domaines: Sciences de l'ingénieur [physics]; Matériaux

Anne Spasojevic - de Biré, Aziza Ikni, Nouha El Hassan, Bertrand Clair, Philippe Scouflaire, et al.. From photochemical and non-photochemical nucleation induced by LASER to experimental and theoretical interaction energy determination: Carbamazepine III a complete study. Serbian Crystallographic Meeting, Jun 2013, Beograd, Serbia. ⟨hal-02302658⟩