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Rodrigues MA, Rego P, Geraldes V, et al. Mannitol Crystallization at Sub-Zero Temperatures: Time/Temperature-Resolved Synchrotron X-ray Diffraction Study and the Phase Diagram. J Phys Chem Lett. 2021;12(5):1453-1460doi: 10.1021/acs.jpclett.0c03680.
Rodrigues, M. A., Rego, P., Geraldes, V., Connor, L. E., Oswald, I. D. H., Sztucki, M., & Shalaev, E. (2021). Mannitol Crystallization at Sub-Zero Temperatures: Time/Temperature-Resolved Synchrotron X-ray Diffraction Study and the Phase Diagram. The journal of physical chemistry letters, 12(5), 1453-1460. https://doi.org/10.1021/acs.jpclett.0c03680
Rodrigues, Miguel A, et al. "Mannitol Crystallization at Sub-Zero Temperatures: Time/Temperature-Resolved Synchrotron X-ray Diffraction Study and the Phase Diagram." The journal of physical chemistry letters vol. 12,5 (2021): 1453-1460. doi: https://doi.org/10.1021/acs.jpclett.0c03680
Rodrigues MA, Rego P, Geraldes V, Connor LE, Oswald IDH, Sztucki M, Shalaev E. Mannitol Crystallization at Sub-Zero Temperatures: Time/Temperature-Resolved Synchrotron X-ray Diffraction Study and the Phase Diagram. J Phys Chem Lett. 2021 Feb 11;12(5):1453-1460. doi: 10.1021/acs.jpclett.0c03680. Epub 2021 Feb 01. PMID: 33523661.
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J Phys Chem Lett. 2021 Feb 11;12(5):1453-1460. doi: 10.1021/acs.jpclett.0c03680. Epub 2021 Feb 01.

Mannitol Crystallization at Sub-Zero Temperatures: Time/Temperature-Resolved Synchrotron X-ray Diffraction Study and the Phase Diagram.

The journal of physical chemistry letters

Miguel A Rodrigues, Pedro Rego, Vitor Geraldes, Lauren E Connor, Iain D H Oswald, Michael Sztucki, Evgenyi Shalaev

Affiliations

  1. Centro de Química Estrutural, Instituto Superior Tecnico, University of Lisbon, Lisbon, Portugal.
  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, U.K.
  3. Collaborative International Research Programme: University of Strathclyde and Nanyang Technological University, Singapore, Technology Innovation Centre, 99 George Street, Glasgow G1 1RD, U.K.
  4. European Synchrotron Radiation Facility, 71 avenue des Martyrs, 38043 Grenoble, Cedex 9, France.
  5. Pharmaceutical Sciences, Abbvie, 2525 Dupont Drive, Irvine, California 92612, United States.

PMID: 33523661 DOI: 10.1021/acs.jpclett.0c03680

Abstract

Mannitol, a common pharmaceutical ingredient, exhibits complex polymorphism even in simple binary mannitol/water mixtures, with four crystalline forms observed. In this investigation, time/temperature-resolved synchrotron X-ray diffraction measurements are performed during freezing and thawing of mannitol/water mixtures. Mannitol crystallization depends strongly on the cooling rate and is initiated during cooling, if the cooling rate is lower than the critical cooling rate; otherwise, mannitol remains amorphous during freezing and crystallizes during subsequent heating above -30 °C. A temperature-composition phase diagram is constructed, reflecting eutectic and peritectic points and lower-temperature equilibria involving mannitol hemihydrate, hexagonal ice, and β-mannitol. Comparison of the experimental data with the phase diagram reveals that the mannitol crystallization behavior does not follow the equilibrium but appears to obey the Ostwald crystallization rule. Novel insights on equilibrium and kinetics phase relationships in mannitol/water systems could lead to improved formulations and manufacturing processes for pharmaceuticals and biopharmaceuticals.

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