title: Crystallization of Carbamazepine in Proximity to Its Precursor Iminostilbene and a Silica Surface.
abstract: Amorphous films of the anticonvulsant drug carbamazepine are easily accessible by various methods, while the crystallization into specific polymorphs represents a challenging and time-consuming task. In this work, the crystallization of drop cast carbamazepine at silica surfaces is investigated by atomic force microscopy and bothin situandex situgrazing incidence X-ray diffraction. The pristine films grow with low crystallization rates into a triclinic polymorph, exhibiting poor orientational order within films. However, if iminostilbene, a chemical precursor of carbamazepine, is added to the solution, enhanced crystallization rates result. The individual components crystallize phase-separated upon solvent evaporation without the formation of cocrystals. Iminostilbene reduces the time scale of carbamazepine crystallization from several hours to minutes. Besides the change in crystallization dynamics, iminostilbene induces order to the carbamazepine crystallites, evident as a 110 texture.In situdata of intermixed solutions demonstrate that iminostilbene crystallization occurs first. The iminostilbene crystals then act as templates for carbamazepine growth, whereby fully epitaxial growth is suggested from the results. The findings motivate such an approach for other systems, as this solution-processed, intrinsic epitaxial behavior might be employed in up-scaled manufacturing processes.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University Graz, 8010 Graz, Austria; Institute of Solid State Physics, Graz University of Technology, 8010 Graz, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Christian
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University Graz , 8010 Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Röthel
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University Graz , 8010 Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Tazreiter
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University Graz, 8010 Graz, Austria; BioTechMed, 8010 Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Department of Physics, Humboldt-Universität zu Berlin , 12489 Berlin, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Salzmann
authors.affiliation: Institute of Solid State Physics, Graz University of Technology, 8010 Graz, Austria; BioTechMed, 8010 Graz, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Resel
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University Graz, 8010 Graz, Austria; BioTechMed, 8010 Graz, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werzer