Christian Paul, Röthel Christian, Tazreiter Martin, Zimmer Andreas, Salzmann Ingo, Resel Roland, Werzer Oliver
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.
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University Graz , 8010 Graz, Austria.
Cryst Growth Des. 2016 May 4;16(5):2771-2778. doi: 10.1021/acs.cgd.6b00090. Epub 2016 Mar 30.
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 both and grazing 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. data 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.
抗惊厥药物卡马西平的非晶薄膜可通过多种方法轻松制备,而结晶为特定多晶型物则是一项具有挑战性且耗时的任务。在这项工作中,通过原子力显微镜以及掠入射X射线衍射研究了滴铸在二氧化硅表面的卡马西平的结晶过程。原始薄膜以低结晶速率生长为三斜多晶型物,在薄膜内表现出较差的取向有序性。然而,如果将卡马西平的化学前体亚氨基芪添加到溶液中,则会提高结晶速率。在溶剂蒸发时,各个组分结晶相分离,不会形成共晶体。亚氨基芪将卡马西平结晶的时间尺度从数小时缩短至数分钟。除了结晶动力学的变化外,亚氨基芪还使卡马西平微晶产生有序性,表现为110织构。混合溶液的 数据表明亚氨基芪先结晶。然后,亚氨基芪晶体作为卡马西平生长的模板,从结果来看表明是完全外延生长。这些发现促使在其他系统中采用这种方法,因为这种溶液处理的固有外延行为可能会用于大规模制造过程中。