Full text

Turn on search term navigation

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Tafamidis, chemical formula C14H7Cl2NO3, is a drug used to delay disease progression in adults suffering from transthyretin amyloidosis, and is marketed worldwide under different tradenames as a free acid or in the form of its meglumine salt. The free acid (CAS no. 594839-88-0) is reported to crystallize as distinct (polymorphic) crystal forms, the thermal stability and structural features of which remained thus far undisclosed. In this paper, we present—by selectively isolating highly pure batches of Tafamidis Form 1 and Tafamidis Form 4—the full characterization of these solids, in terms of crystal structures (determined using state-of-the-art structural powder diffraction methods) and spectroscopic and thermal properties. Beyond conventional thermogravimetric and calorimetric analyses, variable-temperature X-ray diffraction was employed to measure the highly anisotropic response of these (poly)crystalline materials to thermal stimuli and enabled the determination of the linear and volumetric thermal expansion coefficients and of the related indicatrix. Both crystal phases are monoclinic and contain substantially flat and π-π stacked Tafamidis molecules, arranged as centrosymmetric dimers by strong O-H···O bonds; weaker C-H···N contacts give rise, in both polymorphs, to infinite ribbons, which guarantee the substantial stiffness of the crystals in the direction of their elongation. Complete knowledge of the structural models will foster the usage of full-pattern quantitative phase analyses of Tafamidis in drug and polymorphic mixtures, an important aspect in both the forensic and the industrial sectors.

Details

Title
Thermal and Structural Characterization of Two Crystalline Polymorphs of Tafamidis Free Acid
Author
Masciocchi, Norberto 1   VIAFID ORCID Logo  ; Vincenzo Mirco Abbinante 2 ; Zambra, Marco 1 ; Barreca, Giuseppe 2 ; Zampieri, Massimo 2 

 Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab., Università dell’Insubria, Via Valleggio 11, 22100 Como, Italy 
 Chemessentia s.r.l, Via Bovio 6, 28100 Novara, Italy 
First page
7411
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2734704378
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.