Mannitol crystallization at sub-zero temperatures : time/temperature-resolved synchrotron x-ray diffraction study and the phase diagram
Rodrigues, Miguel A and Rego, Pedro and Geraldes, Vitor and Connor, Lauren E. and Oswald, Iain D. H. and Sztucki, Michael and Shalaev, Evgenyi (2021) Mannitol crystallization at sub-zero temperatures : time/temperature-resolved synchrotron x-ray diffraction study and the phase diagram. Journal of Physical Chemistry Letters, 12 (5). 1453–1460. ISSN 1948-7185 (https://doi.org/10.1021/acs.jpclett.0c03680)
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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.
ORCID iDs
Rodrigues, Miguel A, Rego, Pedro, Geraldes, Vitor, Connor, Lauren E. ORCID: https://orcid.org/0000-0002-4626-8921, Oswald, Iain D. H. ORCID: https://orcid.org/0000-0003-4339-9392, Sztucki, Michael and Shalaev, Evgenyi;-
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Item type: Article ID code: 75455 Dates: DateEvent11 February 2021Published1 February 2021Published Online21 January 2021AcceptedSubjects: Science > Chemistry Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 16 Feb 2021 16:12 Last modified: 02 Dec 2024 01:24 URI: https://strathprints.strath.ac.uk/id/eprint/75455