Mannitol crystallization at sub-zero temperatures : time/temperature-resolved synchrotron x-ray diffraction study and the phase diagram
| Autor: | Iain D. H. Oswald, Evgenyi Shalaev, Michael Sztucki, Miguel Rodrigues, Vítor Geraldes, Lauren Evelyn Connor, Pedro Rego |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Materials science
Thermodynamics 02 engineering and technology 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences 0104 chemical sciences law.invention Amorphous solid Polymorphism (materials science) law Phase (matter) X-ray crystallography medicine General Materials Science QD Mannitol Physical and Theoretical Chemistry Crystallization 0210 nano-technology Phase diagram medicine.drug Eutectic system |
| ISSN: | 1948-7185 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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