Co-crystal polymorphs from a solvent-mediated transformation
Co-crystal polymorphs from a solvent-mediated transformation
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DOI：
10.1021/cg800183v
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发表时间：
2008-07-01
影响因子：
3.8
通讯作者：
Cains, Peter W.
中科院分区：
文献类型：
--
作者：
ter Horst, Joop H.;Cains, Peter W.
当纯结晶组分的干燥混合物悬浮在乙醇中时，卡马西平和异烟酰胺的共晶体可以通过溶剂介导的转化过程形成。首先，针状晶体（II型）生长，而纯晶体成分溶解。最终，板状晶体（I型）以针状晶体为代价生长。单晶结构测定表明，I型由卡马西平的交替二聚体和异烟酰胺的二聚体链组成。晶型II的粉末衍射图和针状形状表明，它最可能与已知的卡马西平和烟酰胺的1：1共晶结构同构，该共晶结构由通过氢键与烟酰胺链连接的卡马西平二聚体组成。在I型和II型中，异烟酰胺的吡啶杂氮不参与氢键。两种共晶结构具有1：1的化学计量比，因此它们是多晶型物。溶剂介导的转化表明，晶型I是室温下稳定的晶型。卡马西平-异烟酰胺在乙醇中的相图显示过量的异烟酰胺对于形成共晶体是最佳的，并且具有1：1化学计量的溶液导致卡马西平晶体或最好的卡马西平和共晶体的混合物。在由纯组分溶解度确定的最佳条件下，溶剂介导转化法是寻找共晶多晶型物的简单而有效的方法。
co-crystals of carbamazepine and isonicotinamide can form through a solvent-mediated transformation process when a dry mixture of the pure crystalline components is suspended in ethanol. First, needle-like crystals (form II) grow while the pure crystalline components dissolve. Eventually plate-like crystals (form I) grow at the expense of the needle-like crystals. Single crystal structure determination showed that form I consists of chains of alternating dimers of carbamazepine and dimers of isonicotinamide. The powder diffraction pattern and the needle-like shape of form II show that it most probably is isostructural to the known 1:1 co-crystal structure of carbamazepine and nicotinamide, consisting of dimers of carbamazepine linked to chains of nicotinamide through hydrogen bonding. In both form I and form II, the pyridine heteronitrogen of isonicotinamide does not participate in hydrogen bonding. Both co-crystal structures have 1:1 stoichiometry, and they are therefore polymorphs. The solvent-mediated transformation showed that form I is the stable form at room temperature. The phase diagram for carbamazepine-isonicotinamide in ethanol shows that an excess of isonicotinamide is optimum to form co-crystals, and that solutions with 1:1 stoichiometry result in carbamazepine crystals or at best mixtures of carbarnazepine and co-crystals. Under optimal conditions, determined by the pure component solubilities, the solvent-mediated transformation method is a simple and effective way of searching for co-crystal polymorphs.