title: The interplay between the paracetamol polymorphism and its molecular structures dissolved in supercritical CO2 in contact with the solid phase: In situ vibration spectroscopy and molecular dynamics simulation analysis.
abstract: The aim of this paper is to characterize the distribution of paracetamol conformers which are dissolved in a supercritical CO2 phase being in equilibrium with their corresponding crystalline form. The quantum calculations and molecular dynamics simulations were used in order to characterize the structure and analyze the vibration spectra of the paracetamol conformers in vacuum and in a mixture with CO2 at various thermodynamic state parameters (p,T). The metadynamics approach was applied to efficiently sample the various conformers of paracetamol. Furthermore, using in situ IR spectroscopy, the conformers that are dissolved in supercritical CO2 were identified and the evolution of the probability of their presence as a functions of thermodynamic condition was quantified while the change in the crystalline form of paracetamol have been monitored by DSC, micro IR and Raman techniques. The DSC analysis as well as micro IR and Raman spectroscopic studies of the crystalline paracetamol show that the subsequent heating up above the melting temperature of the polymorph I of paracetamol and the cooling down to room temperature in the presence of supercritical CO2 induces the formation of polymorph II. The in situ IR investigation shows that two conformers (Conf. 1 and Conf. 2) are present in the phase of CO2 while conformer 3 (Conf. 3) has a high probability to be present after re-crystallization.
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences (RAS), Akademicheskaya str. 1, Ivanovo 153045, Russia.
authors.forename: Roman D
authors.initials: RD
authors.lastname: Oparin
authors.affiliation: Laboratoire de Spectrochimie Infrarouge et Raman (UMR CNRS A8516), Université Lille 1 Sciences et Technologies, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Moreau
authors.affiliation: Laboratoire de Spectrochimie Infrarouge et Raman (UMR CNRS A8516), Université Lille 1 Sciences et Technologies, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: De Walle
authors.affiliation: Dipartimento di Chimica, Biologia e Biotecnologie, Università degli Studi di Perugia, via Elce di Sotto 8, I-06123 Perugia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Paolantoni
authors.affiliation: Laboratoire de Spectrochimie Infrarouge et Raman (UMR CNRS A8516), Université Lille 1 Sciences et Technologies, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Abdenacer
authors.initials: A
authors.lastname: Idrissi
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences (RAS), Akademicheskaya str. 1, Ivanovo 153045, Russia.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kiselev
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D012995:Solubility; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D002245:Carbon Dioxide; D000082:Acetaminophen
keywords: Conformational polymorphism; In situ infrared spectroscopy; Supercritical fluids