Dipharma Francis s.r.l., Baranzate, Milan 20021, Italy.
J Pharm Sci. 2012 Dec;101(12):4481-9. doi: 10.1002/jps.23310. Epub 2012 Sep 16.
Nortriptyline hydrochloride, a tricyclic antidepressant, appears in two different polymorphic forms, only one of which (hereafter, form β) has been previously characterized by single-crystal analysis. Form β is monoclinic, P2(1)/c, with a = 5.070(2), b = 34.088(5), c = 9.976(1) Å, and β = 90.74(2)°. A second crystalline form (the α form) has now been characterized by structural powder diffraction methods (using both laboratory and synchrotron radiation diffraction data). Form α crystallizes in the monoclinic P2/c space group, a = 9.99126(6), b = 5.10021(3), c = 34.1636(1) Å, and β = 98.684(6)°. The thermodynamic relationship between the two forms has been determined by differential scanning calorimetry analysis and variable-temperature thermodiffractometric experiments, revealing that the two forms are monotropically related and form α is more stable. Both phases are characterized by a sequence of hydrogen-bonded N-protonated molecules, which, in the two crystalline environments, adopt the same conformation. The difference between the two crystals can be traced back to the supramolecular arrangement characterized by one-dimensional chains, built by homochiral molecules (for conformationally driven chirality) in the α form, and by enantiomeric ones in the β form. This observation nicely explains why, upon heating, solid-solid interconversion between the two forms does not occur.
盐酸去甲替林，一种三环类抗抑郁药，呈现出两种不同的多晶型形式，只有其中一种（以下简称β形式）以前通过单晶分析进行了表征。β形式为单斜晶系，P2(1)/c，a = 5.070(2)，b = 34.088(5)，c = 9.976(1) Å，β = 90.74(2)°。现在已经通过结构粉末衍射方法（使用实验室和同步辐射衍射数据）对第二种晶型（α形式）进行了表征。α形式结晶在单斜晶 P2/c 空间群中，a = 9.99126(6)，b = 5.10021(3)，c = 34.1636(1) Å，β = 98.684(6)°。通过差示扫描量热法分析和变温热衍射实验确定了两种形式之间的热力学关系，揭示了两种形式是单偏相关的，并且α形式更稳定。两种相都具有一系列氢键合的 N-质子化分子的特征，这些分子在两种结晶环境中采用相同的构象。两种晶体之间的差异可以追溯到由同手性分子（由构象驱动的手性）构建的一维链所表征的超分子排列，在α形式中，由对映异构体构建的一维链所表征的超分子排列。这一观察结果很好地解释了为什么在加热时，两种形式之间的固-固相互转化不会发生。
