Grzesiak Adam L, Matzger Adam J
Department of Chemistry and Marcromolecular Science and Engineering Program, The University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
J Pharm Sci. 2007 Nov;96(11):2978-86. doi: 10.1002/jps.20954.
The selection and discovery of new crystalline forms is a longstanding issue in solid-state chemistry of critical importance because of the effect molecular packing arrangement exerts on materials properties. Polymer-induced heteronucleation has recently been developed as a powerful approach to discover and control the production of crystal modifications based on the insoluble polymer heteronucleant added to the crystallization solution. The selective nucleation and discovery of new crystal forms of the well-studied pharmaceuticals flurbiprofen (FBP) and sulindac (SUL) has been achieved utilizing this approach. For the first time, FBP form III was produced in bulk quantities and its crystal structure was also determined. Furthermore, a novel 3:2 FBP:H(2)O phase was discovered that nucleates selectively from only a few polymers. Crystallization of SUL in the presence of insoluble polymers facilitated the growth of form I single crystals suitable for structure determination. Additionally, a new SUL polymorph (form IV) was discovered by this method. The crystal forms of FBP and SUL are characterized by Raman and FTIR spectroscopies, X-ray diffraction, and differential scanning calorimetry.
新晶型的选择与发现是固态化学中一个长期存在且至关重要的问题，因为分子堆积排列对材料性能有影响。聚合物诱导异相成核法最近已发展成为一种强大的方法，可基于添加到结晶溶液中的不溶性聚合物异质成核剂来发现和控制晶体变体的产生。利用这种方法已实现了对研究充分的药物氟比洛芬（FBP）和舒林酸（SUL）新晶型的选择性成核与发现。首次大量制备出了FBP III型，并确定了其晶体结构。此外，还发现了一种新型的3:2 FBP:H₂O相，它仅从少数几种聚合物中选择性成核。在不溶性聚合物存在下SUL的结晶促进了适合结构测定的I型单晶的生长。此外，通过该方法还发现了一种新的SUL多晶型物（IV型）。FBP和SUL的晶型通过拉曼光谱和傅里叶变换红外光谱、X射线衍射以及差示扫描量热法进行表征。
