Freeze-thaw of Pharmaceutical Solutions: Counter-Intuitive Finding of an Increase in Mechanical Stress between Tg” and Tg’ in Frozen Sucrose/Water Mixtures | Sciact - CRIS-система Института катализа

Freeze-thaw of Pharmaceutical Solutions: Counter-Intuitive Finding of an Increase in Mechanical Stress between Tg” and Tg’ in Frozen Sucrose/Water Mixtures Научная публикация

Журнал

Journal of Pharmaceutical Sciences
ISSN: 0022-3549 , E-ISSN: 1520-6017

Вых. Данные

Год: 2025, Том: 114, Номер: 7, Номер статьи : 103800, Страниц : DOI: 10.1016/j.xphs.2025.103800

Ключевые слова

Aqueous solutions; Freezing; Ice crystals; Microstrain; Size of crystalline domains; Synchrotron X-ray diffraction

Авторы

Kostyuchenko Anastasia ¹ , Zakharov Boris ^2,3 , Fisyuk Alexander ^1,4 , Bhatnagar Bakul ⁵ , Seryotkin Yurii ^3,6 , Boldyreva Elena ³ , Shalaev Evgenyi ⁷

Организации

1	Laboratory of New Organic Materials, Omsk State Technical University, 11 Mira Avenue, Omsk 644050, Russian Federation
2	Synchrotron Radiation Facility SKIF, Boreskov Institute of Catalysis SB RAS, Kol'tsovo, 630559, Russian Federation
3	Novosibirsk State University, Pirogova Street, 2, Novosibirsk 630090, Russian Federation
4	Laboratory of Organic Synthesis, Chemistry Department, Omsk F.M. Dostoevsky State University, Prospect Mira 55a, Omsk, 644053, Russian Federation
5	BTx PharmSci Pharmaceutical R&D, Pfizer, Inc., One Burtt Road, Andover 01810, MA, USA
6	Sobolev Institute of Geology and Mineralogy, Siberian Branch of the RAS, Koptyuga Avenue, 3, Novosibirsk 630090, Russian Federation
7	Development Sciences, R&D, AbbVie Inc., Irvine, CA, USA

Информация о финансировании (4)

1	European Synchrotron Radiation Facility	LS-2601
2	European Synchrotron Radiation Facility	LS-2742
3	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	FWUR-2024-0042
4	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	Приоритет 2030

High-resolution synchrotron X-ray powder diffraction has been utilized to detect mechanical stresses in frozen solutions, via analysis of the profiles of the diffraction peaks of ice. Increase in the width of the peaks (peaks broadening) reflects disruption of the crystal lattice, with contributions including a decrease in the crystallite size and an increase in microstrain. Frozen sucrose solutions (5 and 10 % w/v) were frozen at 100 K and then heated and annealed at -45 °C (228 K) and -15 °C (258 K), i.e. between the two apparent glass transition events in the freeze-concentrated solutions (Tg” and Tg’), and above the Tg’, respectively. A decrease in microstrain and an increase in ice crystallite size were observed during annealing at -15 °C (above the Tg’), which is consistent with Ostwald ripening of ice crystals. Unexpectedly, and for the first time, an opposite trend was observed during annealing at the lower temperature of -45 °C, between Tg” and Tg’. To the best of our knowledge, this is the first report of an increased strain in the crystalline ice domains and of simultaneous size reduction during annealing of frozen aqueous solutions. Considering that the interaction with ice crystals may result in protein destabilization, the size and microstrain of ice crystallites can serve as markers of the freeze/thaw stresses on biopharmaceuticals. A practical implication is that a prolonged hold between Tg” and Tg’ may increase stress imposed on protein molecules, i.e. a lower temperature is not always better for preserving biopolymers when freezing their aqueous solutions.

Kostyuchenko A. , Zakharov B. , Fisyuk A. , Bhatnagar B. , Seryotkin Y. , Boldyreva E. , Shalaev E.
Freeze-thaw of Pharmaceutical Solutions: Counter-Intuitive Finding of an Increase in Mechanical Stress between Tg” and Tg’ in Frozen Sucrose/Water Mixtures
Journal of Pharmaceutical Sciences. 2025. V.114. N7. 103800 . DOI: 10.1016/j.xphs.2025.103800 WOS Scopus CAPlus PMID OpenAlex СКИФ ID

Поступила в редакцию:	6 нояб. 2024 г.
Принята к публикации:	16 апр. 2025 г.
Опубликована online:	23 апр. 2025 г.
Опубликована в печати:	1 июл. 2025 г.

Web of science:	WOS:001493471600004
Scopus:	2-s2.0-105004986582
Chemical Abstracts:	2025:1109103
PMID (PubMed):	40280484
OpenAlex:	W4409717252
СКИФ ID:	3921

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