title: Varenicline L-tartrate crystal forms: characterization through crystallography, spectroscopy, and thermodynamics.
abstract: This research utilized crystallographic, spectroscopic, and thermal analysis data to assess the thermodynamic stability relationship between the three known crystal forms of Varenicline L-tartrate. Of the two anhydrous forms (Forms A and B), Form B was determined to be the stable form at 0 K based on its calculated true density, hydrogen bonding in the crystal lattice, and application of the IR rule. Form A has a higher melting point and higher solubility at room temperature as compared to Form B, indicating that these forms are enantiotropically related. Application of the eutectic-melting method enabled accurate determination of the transition temperature (63 degrees C), with Form B as the stable anhydrous form at room temperature. The stability relationships between the anhydrous polymorphs and the monohydrate (Form C) were assessed through exposure of the anhydrous forms to a range of water vapor pressures at room temperature. A phase boundary was identified, with the monohydrate being the thermodynamically stable form above critical water activity values of 0.85 and 0.94 for Forms A and B, respectively. These results provide a better understanding of the form stability as it relates to normal manufacturing and storage conditions for the active pharmaceutical ingredient and drug product.
authors.affiliation: Materials Science, Pfizer Inc., Eastern Point Road, MS 4051, Groton, Connecticut 06340, USA. brendan.j.murphy@pfizer.com
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Murphy
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Casteel
authors.forename: Ana
authors.initials: A
authors.lastname: Cobani
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Krzyzaniak
mesh_terms: D003461:Crystallography; D004304:Dosage Forms; D012995:Solubility; D013057:Spectrum Analysis; D013644:Tartrates; D013816:Thermodynamics; D044366:Transition Temperature; D014867:Water / Q000737:chemistry*
chemical_list: D004304:Dosage Forms; D013644:Tartrates; D014867:Water; C029768:tartaric acid