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Impact of secondary ice in a frozen NaCl freeze-concentrated solution on the extent of methylene blue aggregation

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VESELÝ Lukáš ZAVACKA Kamila ŠTŮSEK Radim OLBERT Martin NEDELA Vilem SHALAEV Evgenyi HEGER Dominik

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj International Journal of Pharmaceutics
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://www.sciencedirect.com/science/article/pii/S0378517323011134?via%3Dihub
Doi http://dx.doi.org/10.1016/j.ijpharm.2023.123691
Klíčová slova Freezing; Lyophilization; Methylene blue; Ice morphology; Secondary ice; Freeze-concentrated solution
Popis 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.
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