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@article{2371521,
author = {Veselý, Lukáš and Zavacka, Kamila and Štůsek, Radim and Olbert, Martin and Nedela, Vilem and Shalaev, Evgenyi and Heger, Dominik},
article_location = {AMSTERDAM},
article_number = {JAN},
doi = {http://dx.doi.org/10.1016/j.ijpharm.2023.123691},
keywords = {Freezing; Lyophilization; Methylene blue; Ice morphology; Secondary ice; Freeze-concentrated solution},
language = {eng},
issn = {0378-5173},
journal = {International Journal of Pharmaceutics},
title = {Impact of secondary ice in a frozen NaCl freeze-concentrated solution on the extent of methylene blue aggregation},
url = {https://www.sciencedirect.com/science/article/pii/S0378517323011134?via%3Dihub},
volume = {650},
year = {2024}
}
TY - JOUR
ID - 2371521
AU - Veselý, Lukáš - Zavacka, Kamila - Štůsek, Radim - Olbert, Martin - Nedela, Vilem - Shalaev, Evgenyi - Heger, Dominik
PY - 2024
TI - Impact of secondary ice in a frozen NaCl freeze-concentrated solution on the extent of methylene blue aggregation
JF - International Journal of Pharmaceutics
VL - 650
IS - JAN
SP - 123691
EP - 123691
PB - ELSEVIER
SN - 03785173
KW - Freezing
KW - Lyophilization
KW - Methylene blue
KW - Ice morphology
KW - Secondary ice
KW - Freeze-concentrated solution
UR - https://www.sciencedirect.com/science/article/pii/S0378517323011134?via%3Dihub
N2 - Freezing and lyophilization have been utilized for decades to stabilize pharmaceutical and food products. Freezing a solution that contains dissolved salt and/or organic matter produces pure primary ice crystal grains separated by freeze-concentrated solutions (FCS). The microscopic size of the primary ice crystals depends on the cooling conditions and the concentration of the solutes. It is generally accepted that primary ice crystals size influences the rate of sublimation and also can impact physico-chemical behaviour of the species in the FCS. This article, however, presents a case where the secondary ice formed inside the FCS plays a critical role. We microscoped the structures of ice-cast FCS with an environmental scanning electron microscope and applied the aggregation-sensitive spectroscopic probe methylene blue to determine how the microstructure affects the mo-lecular arrangement. We show that slow cooling at-50 degrees C produces large salt crystals with a small specific surface, resulting in a high degree of molecular aggregation within the FCS. In contrast, fast liquid nitrogen cooling yields an ultrafine structure of salt crystals having a large specific surface area and, therefore, inducing smaller aggregation. The study highlights a critical role of secondary ice in solute aggregation and introduces methylene blue as a molecular probe to investigate freezing behaviour of aqueous systems with crystalline solute.
ER -
VESELÝ, Lukáš, Kamila ZAVACKA, Radim ŠTŮSEK, Martin OLBERT, Vilem NEDELA, Evgenyi SHALAEV and Dominik HEGER. Impact of secondary ice in a frozen NaCl freeze-concentrated solution on the extent of methylene blue aggregation. \textit{International Journal of Pharmaceutics}. AMSTERDAM: ELSEVIER, 2024, vol.~650, JAN, p.~123691-123700. ISSN~0378-5173. Available from: https://dx.doi.org/10.1016/j.ijpharm.2023.123691.
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