Hartman P, Chan H K
Department of Geochemistry, State University of Utrecht, The Netherlands.
Pharm Res. 1993 Jul;10(7):1052-8. doi: 10.1023/a:1018927109487.
The habit (external morphology) of a crystal is controlled by both the external (environmental) conditions of crystallization and the internal (structural) factors of the crystal. In order to separate the effects of the crystal structure and of the solvent and other external factors on the experimentally observed growth habit, the theoretical habit can be derived from the crystal structure using the periodic bond chain (PBC) theory and attachment energy considerations. According to the PBC theory the crystal habit is governed by a set of uninterrupted chains of strong bonds formed in the crystal lattice. In addition, the attachment energy (E(att)) is defined as the energy released per mole when a new layer is deposited on a crystal face. Since the habit of a crystal is determined by the relative growth rate (R) of the various faces, by taking R proportional to E(att), the theoretical habit can thus be derived from E(att). Using this approach, we obtained the theoretical crystal habit of an antitumor drug, hexamethylmelamine (HMM). The possible effect of solvents on the habit modification of HMM is discussed. This technique, based purely on the knowledge of the crystal structure, is directly applicable to other pharmaceuticals in deriving their theoretical crystal habit.
晶体的习性（外部形态）受结晶的外部（环境）条件和晶体的内部（结构）因素共同控制。为了区分晶体结构以及溶剂和其他外部因素对实验观察到的生长习性的影响，可以利用周期键链（PBC）理论和附着能考量，从晶体结构推导出理论习性。根据PBC理论，晶体习性由晶格中形成的一组不间断的强键链决定。此外，附着能（E(att)）定义为在晶体表面沉积新层时每摩尔释放的能量。由于晶体习性由各个晶面的相对生长速率（R）决定，通过使R与E(att)成正比，因此可以从E(att)推导出理论习性。采用这种方法，我们获得了一种抗肿瘤药物六甲基三聚氰胺（HMM）的理论晶体习性。讨论了溶剂对HMM习性改变的可能影响。这种完全基于晶体结构知识的技术，可直接应用于推导其他药物的理论晶体习性。
