Acidity changes in glycine and L-histidine buffers, mannitol,
and their mixtures after freezing and lyophilization

J 2026

Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization

VESELÝ, Lukáš; Jan RYŠÁVKA; Radim ŠTŮSEK; Susrisweta BEHERA; Jiří ZEMAN et al.

Základní údaje

Originální název

Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization

Autoři

VESELÝ, Lukáš; Jan RYŠÁVKA; Radim ŠTŮSEK; Susrisweta BEHERA; Jiří ZEMAN ; Thomas LOERTING a Dominik HEGER

Vydání

INTERNATIONAL JOURNAL OF PHARMACEUTICS, AMSTERDAM, ELSEVIER, 2026, 0378-5173

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.200 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

FROZEN AQUEOUS-SOLUTIONS; SCANNING-ELECTRON-MICROSCOPE; PH CHANGES; PROTEIN FORMULATIONS; RECIPROCAL SYSTEM; PHYSICAL STATE; GAMMA-GLYCINE; CRYSTALLIZATION; ICE

Štítky

14313010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 2. 2026 11:32, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Freezing and lyophilization are commonly used methods for stabilizing pharmaceutical and biochemical formulations. However, these processes can introduce a variety of freezing-induced stresses that may lead not to stabilization, but rather to the destabilization of active molecules. One of the most significant of these stresses is freezing-induced acidity change, which has been shown to cause protein aggregation, loss of structural integrity, and increased chemical reactivity. While buffers are routinely used in liquid formulations to minimize pH fluctuations, several studies have demonstrated that certain buffers not only fail to maintain pH during freezing but may actively contribute to acidity shifts. In this study, we investigate the effects of cooling rate, initial pH, mannitol concentration, and lyophilization on acidity in glycine and L-histidine buffer systems in the solid state (both frozen and lyophilized) using UV-VIS spectroscopy and differential scanning calorimetry. Our results indicate that the freezing of amino acid buffers causes a slight increase in pH (basification); however, changes in acidity are not solely the consequence of freezing as they also occur during lyophilization. Notably, in L-histidine with mannitol at pH 7, lyophilization induces acidification of up to 4 units-opposite to the direction observed during freezing. Furthermore, we explore the correlation between vitrification of the freeze-concentrated solution and freezing-induced acidity changes, as quantified using the Hammett acidity function (H2-). These findings may inform the rational design of more robust stabilization strategies.

Návaznosti

GA25-15358S, projekt VaV

Název: Spektroskopické studie environmentálně významných látek ve vysoce koncentrovaných roztocích

Investor: Grantová agentura ČR, Spektroskopické studie environmentálně významných látek ve vysoce koncentrovaných roztocích

Citovat

VESELÝ, Lukáš; Jan RYŠÁVKA; Radim ŠTŮSEK; Susrisweta BEHERA; Jiří ZEMAN; Thomas LOERTING a Dominik HEGER. Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization. INTERNATIONAL JOURNAL OF PHARMACEUTICS. AMSTERDAM: ELSEVIER, 2026, roč. 691, FEB, s. 1-17. ISSN 0378-5173. Dostupné z: https://doi.org/10.1016/j.ijpharm.2026.126584.

@article{2553679,
   author = {Veselý, Lukáš and Ryšávka, Jan and Štůsek, Radim and Behera, Susrisweta and Zeman, Jiří and Loerting, Thomas and Heger, Dominik},
   article_location = {AMSTERDAM},
   article_number = {FEB},
   doi = {https://doi.org/10.1016/j.ijpharm.2026.126584},
   keywords = {FROZEN AQUEOUS-SOLUTIONS; SCANNING-ELECTRON-MICROSCOPE; PH CHANGES; PROTEIN FORMULATIONS; RECIPROCAL SYSTEM; PHYSICAL STATE; GAMMA-GLYCINE; CRYSTALLIZATION; ICE},
   language = {eng},
   issn = {0378-5173},
   journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS},
   title = {Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization},
   url = {https://www.sciencedirect.com/science/article/pii/S0378517326000323?via%3Dihub},
   volume = {691},
   year = {2026}
}

TY  - JOUR
ID  - 2553679
AU  - Veselý, Lukáš - Ryšávka, Jan - Štůsek, Radim - Behera, Susrisweta - Zeman, Jiří - Loerting, Thomas - Heger, Dominik
PY  - 2026
TI  - Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization
JF  - INTERNATIONAL JOURNAL OF PHARMACEUTICS
VL  - 691
IS  - FEB
SP  - 1-17
EP  - 1-17
PB  - ELSEVIER
SN  - 03785173
KW  - FROZEN AQUEOUS-SOLUTIONS
KW  - SCANNING-ELECTRON-MICROSCOPE
KW  - PH CHANGES
KW  - PROTEIN FORMULATIONS
KW  - RECIPROCAL SYSTEM
KW  - PHYSICAL STATE
KW  - GAMMA-GLYCINE
KW  - CRYSTALLIZATION
KW  - ICE
UR  - https://www.sciencedirect.com/science/article/pii/S0378517326000323?via%3Dihub
N2  - Freezing and lyophilization are commonly used methods for stabilizing pharmaceutical and biochemical formulations. However, these processes can introduce a variety of freezing-induced stresses that may lead not to stabilization, but rather to the destabilization of active molecules. One of the most significant of these stresses is freezing-induced acidity change, which has been shown to cause protein aggregation, loss of structural integrity, and increased chemical reactivity. While buffers are routinely used in liquid formulations to minimize pH fluctuations, several studies have demonstrated that certain buffers not only fail to maintain pH during freezing but may actively contribute to acidity shifts. In this study, we investigate the effects of cooling rate, initial pH, mannitol concentration, and lyophilization on acidity in glycine and L-histidine buffer systems in the solid state (both frozen and lyophilized) using UV-VIS spectroscopy and differential scanning calorimetry. Our results indicate that the freezing of amino acid buffers causes a slight increase in pH (basification); however, changes in acidity are not solely the consequence of freezing as they also occur during lyophilization. Notably, in L-histidine with mannitol at pH 7, lyophilization induces acidification of up to 4 units-opposite to the direction observed during freezing. Furthermore, we explore the correlation between vitrification of the freeze-concentrated solution and freezing-induced acidity changes, as quantified using the Hammett acidity function (H2-). These findings may inform the rational design of more robust stabilization strategies.
ER  -

VESELÝ, Lukáš; Jan RYŠÁVKA; Radim ŠTŮSEK; Susrisweta BEHERA; Jiří ZEMAN; Thomas LOERTING a Dominik HEGER. Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization. \textit{INTERNATIONAL JOURNAL OF PHARMACEUTICS}. AMSTERDAM: ELSEVIER, 2026, roč.~691, FEB, s.~1-17. ISSN~0378-5173. Dostupné z: https://doi.org/10.1016/j.ijpharm.2026.126584.

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