title: A structural powder diffraction study of two polymorphic forms of nortriptyline hydrochloride.
abstract: 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.
authors.affiliation: Dipharma Francis s.r.l., Baranzate, Milan 20021, Italy. chiara.vladiskovic@dipharma.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Vladiskovic
authors.forename: Norberto
authors.initials: N
authors.lastname: Masciocchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cervellino
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000737:chemistry*; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D007536:Isomerism; D008958:Models, Molecular; D009661:Nortriptyline / Q000737:chemistry*; D033362:Powder Diffraction; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D009661:Nortriptyline