Beiner M, Rengarajan G T, Pankaj S, Enke D, Steinhart M
Martin-Luther-Universität Halle-Wittenberg, Institut für Physik, D-06099 Halle/Saale, Germany. beiner@ physik.uni-halle.de
Nano Lett. 2007 May;7(5):1381-5. doi: 10.1021/nl0705081. Epub 2007 Apr 17.
We show that nanoconfinement is a handle to rationally produce and stabilize otherwise metastable or transient polymorphs of pharmaceuticals, as required for controllable and efficient drug delivery. The systematic investigation of crystallization under confinement unveils thermodynamic properties of metastable polymorphs not accessible otherwise and may enhance the understanding of the crystallization behavior of pharmaceuticals in general. As an example in this case, we studied acetaminophen confined to inexpensive and biocompatible nanoporous host systems. Calorimetric and X-ray scattering data clearly evidence that either the stable polymorph form I or the metastable polymorph form III can be stabilized in high yields. Thermodynamic parameters for form III of acetaminophen are reported, and strategies to manipulate the crystalline state in pores by thermal treatments are presented.
我们表明，纳米限域是一种合理制备和稳定药物其他亚稳或瞬态多晶型物的方法，这是可控高效药物递送所必需的。对限域条件下结晶的系统研究揭示了亚稳多晶型物无法通过其他方式获得的热力学性质，并可能增强对药物结晶行为的总体理解。在这种情况下，作为一个例子，我们研究了对乙酰氨基酚在廉价且生物相容的纳米多孔主体系统中的限域情况。量热和X射线散射数据清楚地证明，稳定的I型多晶型物或亚稳的III型多晶型物都可以高产率地得到稳定。报道了对乙酰氨基酚III型的热力学参数，并提出了通过热处理来控制孔内晶态的策略。
