Experimental Demonstration of the Carbamazepine Crystallization from Non-photochemical Laser-Induced Nucleation in Acetonitrile and Methanol

Abstract

International audienceThis paper reports for the first time the crystallization of the carbamazepine (CBZ) molecule in two solvents (methanol and acetonitrile) using the non-photochemical laser-induced nucleation (NPLIN) technique. The metastable zone of CBZ is first determined experimentally for different temperatures in both solvents. Then, the prepared solutions are irradiated by a 532 nm wavelength nanosecond pulsed laser and permitted to obtain CBZ crystals of phases I and III. The impact of laser power and polarization (circularly (CP) and linearly (LP)) on the CBZ crystallization efficiency in both solvents is determined through experiments. According to the results, the crystallization efficiency is significantly higher in methanol than in acetonitrile, and it is higher in solutions irradiated by CP laser than those by LP laser. Moreover, the irradiation of an acetonitrile solution by a LP laser results in CBZ phases I and III, whereas irradiation by the CP laser leads to CBZ phase III crystals. An ab initio determination of the interaction energy of different pairs of CBZ has been carried-out that enables the explanation of the nucleation in acetonitrile for both polarizations. In methanol, only CBZ phase III is obtained, which is in agreement with the ability of methanol to create noncovalent interactions preventing the CBZ phase I and II nucleation

Polarization independence of laser-induced nucleation in supersaturated aqueous urea solutions

“…For some other smallmolecule systems, the ellipticity of polarization appears to influence the polymorph obtained. [11][12][13][14] In the case of glycine, we note that results from different groups do not agree on the fraction of g-glycine obtained at different supersaturations. 11,26,27 However, this may be due to different experimental conditions.…”

“…10 It was later noted that complete binary control between the two polymorphs occurred only within a small window of supersaturation (146-155%). 11 The influence of the polarization of light on product crystal polymorph through NPLIN has been observed for glycine, 10 L-histidine, 12 carbamazepine, 13 and sulfathiazole. 14 Several reports have questioned the feasibility of the OKE mechanism for NPLIN.…”

Laser-induced nucleation of carbon dioxide bubbles

“…NPLIN has been observed for a range of solutes including inorganic salts, small organic molecules, a) e-mail: andrew.alexander@ed.ac.uk pure liquids, and proteins. 5 The mechanism for NPLIN is thought to rely on formation of pre-nucleating clusters of solute that become stabilized in the strong, transient electric field of a pulse of laser light. 3,6,7 In the case of small organic molecules, a Kerr effect at optical frequencies is thought to align clustered molecules relative to the electric field.…”

Supersaturation dependence of glycine polymorphism using laser-induced nucleation, sonocrystallization and nucleation by mechanical shock

“…In a study on carbamazepine, Ikni et al saw a preference for form I using LP light with acetonitrile as solvent, but not when using methanol as solvent. 61 Experiments on NPLIN of sulfathiazole in water/ethanol (v/v 1 : 1) showed a clear bias towards form IV with LP light, and form III with CP light. 62 These studies do suggest that the polarization of light can influence nucleation.…”