Ice Recrystallization in a Solution of a Cryoprotector and Its Inhibition by a Protein: Synchrotron X-Ray Diffraction Study

Boris Zakharov, Alexander Fisyuk, Andy Fitch, Yves Watier, Anastasia Kostyuchenko, Dushyant Varshney, Michael Sztucki, Elena Boldyreva, Evgenyi Shalaev

Результат исследования: Научные публикации в периодических изданияхстатья

7 Цитирования (Scopus)

Аннотация

Ice formation and recrystallization is a key phenomenon in freezing and freeze-drying of pharmaceuticals and biopharmaceuticals. In this investigation, high-resolution synchrotron X-ray diffraction is used to quantify the extent of disorder of ice crystals in binary aqueous solutions of a cryoprotectant (sorbitol) and a protein, bovine serum albumin. Ice crystals in more dilute (10 wt%) solutions have lower level of microstrain and larger crystal domain size than these in more concentrated (40 wt%) solutions. Warming the sorbitol–water mixtures from 100 to 228 K resulted in partial ice melting, with simultaneous reduction in the microstrain and increase in crystallite size, that is, recrystallization. In contrast to sorbitol solutions, ice crystals in the BSA solutions preserved both the microstrain and smaller crystallite size on partial melting, demonstrating that BSA inhibits ice recrystallization. The results are consistent with BSA partitioning into quasi-liquid layer on ice crystals but not with a direct protein–ice interaction and protein sorption on ice surface. The study shows for the first time that a common (i.e., not-antifreeze) protein can have a major impact on ice recrystallization and also presents synchrotron X-ray diffraction as a unique tool for quantification of crystallinity and disorder in frozen aqueous systems.

Язык оригиналаанглийский
Страницы (с-по)2129-2138
Число страниц10
ЖурналJournal of Pharmaceutical Sciences
Том105
Номер выпуска7
DOI
СостояниеОпубликовано - 1 июл 2016

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