Abstract
Three crystal forms of iopamidol, an iodinated contrast media used in radiology, have been so far elucidated: an anhydrous, a monohydrate and a pentahydrate form (labeled hereafter as W0, W1 and W5, respectively), which showed the occurrence of different conformations, atropisomeric in nature. Specifically, the anhydrous and monohydrate forms contain iopamidol with a “syn” conformation of the two symmetric sidearms, while an “anti” conformation was found in the pentahydrate, making it a conformational (pseudo)-polymorph of the first two. The three crystal forms have been here investigated by means of DSC, variable temperature X-ray powder diffraction and Raman spectroscopy. This study enabled us to highlight the thermal-induced transformations, leading to the discovery of new crystal forms, for a total of four hydrated and four distinct anhydrous phases. In particular, the DSC curve of W0 revealed only a reversible solid–solid transition at around 180 °C before melting, with subsequent degradation above 300 °C. W1, after the loss of lattice water around 100 °C, shows a characteristic split peak at about 250 °C, which is attributed to melting. Below 150 °C, powder diffraction of W1 suffers of minor changes, with a smooth variation of the lattice parameters, in agreement with a progressive loss of water in a reversible event, monitored also by DSC. At variance, W5 evidenced an irreversible loss of water in three distinct steps, for three, one and one H2O molecules each, respectively; subsequent transitions occur at 140 and 180 °C, before melting at 240 °C. Three clearly visible transformations were also detected by variable temperature powder diffraction measurements, where the loss of three molecules of water in a single step, generating a bis-hydrated species (W2), is followed by a second dehydration process leading, above 75 °C, to a new monohydrate phase W1′, different from the known W1 form. The Raman spectra of the three crystal forms, measured upon heating up to 160 °C, evidenced changes in spectral regions of amides that, according to our simulations of the vibrational properties, can be attributed to changes of the hydration properties and, more significantly, in terms of the “syn” and “anti” conformations.
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Krause W, Schneider PW. Chemistry of X-ray contrast agents. In: Krause W, editor. Contrast agents II: optice, ultrasound, X-ray and radiopharmaceutical imaging. Topics in current chemistry. Berlin: Springer; 2002. p. 107–50.
Bonnemain B, Meyer D, Schaefer M, Dugast-Zrihen M, Legreneur S, Doucet D. New iodinated low-osmolar contrast media: a revised concept of hydrophilicity. Invest Radiol. 1990;25:S104–6.
Krasuski RA, Sketch MH, Harrison JK. Contrast agents for cardiac angiography: osmolality and contrast complications. Curr Interv Cardiol Rep. 2000;2:258–66.
Bonati F, Felder E, Tirone P. Iopamidol: new preclinical and clinical data. Invest Radiol. 1980;15:S310–6.
Drayer BP, Warner MA, Sudilovsky A, Luther J, Wilkins R, Allen S, et al. Iopamidol vs metrizamide: a double blind study for cervical myelography. Neuroradiology. 1982;24:77–84.
Felder E, Grandi M, Pitrè D, Vittadini G. Iopamidol. In: Florey K, editor. Analytical profiles of drug substances, vol. 17. San Diego: Academic Press; 1988. p. 115–54.
Ganazzoli F, Albinati A, Pitrè D. Iopamidol, C17H22I3N3O8. Acta Crystallogr C. 1983;39:1570–2.
Bellich B, Di Fonzo S, Tavagnacco L, Paolantoni M, Masciovecchio C, Bertolotti F, Giannini G, De Zorzi R, Geremia S, Maiocchi A, Uggeri F, Masciocchi N, Cesàro A. Myelography iodinated contrast media. II. Conformational versatility of iopamidol in the solid state. Mol Pharm. 2017;14:468–77.
Fontanive L, D’Amelio N, Cesàro A, Gamini A, Tavagnacco L, Paolantoni M, Brady JW, Maiocchi A, Uggeri F. Myelography iodinated contrast media. I. Unraveling the atropisomerism properties in solution. Mol Pharm. 2015;12:1939–50.
Giron D. Investigations of polymorphism and pseudo-polymorphism in pharmaceuticals by combined thermoanalytical techniques. J Therm Anal Calorim. 2001;64:37–60.
Kawakami K. Reversibility of enantiotropically related polymorphic transformations from a practical viewpoint: thermal analysis of kinetically reversible/irreversible polymorphic transformations. J Pharm Sci. 2007;96:982–9.
Malpezzi L, Fuganti C, Maccaroni E, Masciocchi N, Nardi A. Thermal and structural characterization of two polymorphs of Atovaquone and of its chloro derivative. J Therm Anal Calorim. 2010;102:203–10.
Terada K, Kurobe H, Ito M, Yoshihashi Y, Yonemochi E, Fujii K, Uekusa H. Polymorphic and pseudomorphic transformation behavior of acyclovir based on thermodynamics and crystallography. J Therm Anal Calorim. 2013;113:1261–7.
Faroongsarng D. Theoretical aspects of differential scanning calorimetry as a tool for the studies of equilibrium thermodynamics in pharmaceutical solid phase transitions. AAPS PharmSciTech. 2016;17:1–6.
Brandel C, Amharar Y, Rollinger JM, Griesser UJ, Cartigny Y, Petit S, Coquerel G. Impact of molecular flexibility on double polymorphism, solid solutions and chiral discrimination during crystallization of diprophylline enantiomers. Mol Pharm. 2013;10:3850–61.
Coquerel G, Tamura R. Enantiomeric disorder pharmaceutically oriented. In: Descamps M, editor. Disordered pharmaceutical materials. Weinheim: Wiley-VCH; 2016. p. 135–59.
Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14:33–8.
Willart JF, Descamps M. Solid state amorphization of pharmaceuticals. Mol Pharm. 2008;5:905–20.
TOPAS-R, V. 3.0, Bruker AXS, 2005, Karlsruhe, Germany.
Cheary RW, Coelho A. A fundamental parameters approach to X-ray line-profile fitting. J Appl Cryst. 1992;25:109–21.
D’Amico F, Saito M, Bencivenga F, Marsi M, Gessini A, Camisasca G, Principi E, Cucini R, Di Fonzo S, Battistoni A, Giangrisostomi E, Masciovecchio C. UV Resonant Raman Scattering Facility at Elettra. Nucl Instrum Methods Phys Res A. 2013;703:33–7.
Sussich F, Skopec C, Brady JW, Cesàro A. Reversible dehydration of trehalose and anhydrobiosis: from solution state to an exotic crystal? Carbohydr Res. 2001;334:165–76.
Furuki T, Kishi A, Sakurai M. De-and rehydration behavior of α,α-trehalose dihydrate under humidity-controlled atmospheres. Carbohydr Res. 2005;340:429–38.
Pina MF, Pinto JF, Sousa JJ, Fábián L, Zhao M, Craig DQ. Identification and characterization of stoichiometric and nonstoichiometric hydrate forms of paroxetine HCl: reversible changes in crystal dimensions as a function of water absorption. Mol Pharm. 2012;9:3515–25.
Tangeman JA, Lange RA. Determination of the limiting fictive temperature of silicate glasses from calorimetric and dilatometric methods: application to low-temperature liquid volume measurements. Am Mineral. 2001;86:1331–44.
Dollish FG, Fately WG, Bentley FF. Characteristic Raman frequencies of organic compounds. New York: Wiley; 1974.
Das D, Jacobs T, Barbour LJ. Exceptionally large positive and negative anisotropic thermal expansion of an organic crystalline material. Nat Mater. 2010;9:36–9.
Vippagunta SR, Brittain HG, Grant DJ. Crystalline solids. Adv Drug Deliv Rev. 2001;48:3–26.
Acknowledgements
Research carried out in the framework of a collaboration between the University of Trieste and the Bracco Research Center under the Project “Physical Chemistry of Iodinated Contrast Media.” G. Giannini is acknowledged for some preliminary calorimetric measurements. Partial financial support to F.B. by Federchimica (Milan, Italy) and support for computational work by CINECA ISCRA grants (Bologna, Italy) is gratefully acknowledged.
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Bellich, B., Bertolotti, F., Di Fonzo, S. et al. Thermal properties of iopamidol. J Therm Anal Calorim 130, 413–423 (2017). https://doi.org/10.1007/s10973-017-6409-y
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DOI: https://doi.org/10.1007/s10973-017-6409-y