Physical and chemical changes in Alhydrogel™ damaged by freezing

Kurzątkowski, W; Kartoğlu, Ümit; Górska, Paulina; Główka, Małgorzata; Woźnica, Katarzyna; Zasada, Aleksandra Anna; Szczepańska, Grażyna; Trykowski, Grzegorz; Gniadek, Marianna; Donten, Mikołaj

doi:10.1016/j.vaccine.2018.10.023

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…Units of optical absorbance changes per time are used when the SR is measured via monitoring of the ultraviolet absorption of the supernatant layer [12]. In some cases, the SR is expressed as the time of completion of the sedimentation process—until no further changes in the height (thickness) of a sediment were observed [13]. This divergence of units for SR s measured by different techniques perhaps reflects that only relative values are needed for comparing different pharmaceutical suspension formulations of the same API.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation

Taraban

2020

Magnetic Reson in Chemistry

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Suspensions of solid particles find applications in many areas—mining, waste treatment, and in pharmaceutical formulations. Pharmaceutical suspensions include aluminum‐adjuvanted vaccines are widely administered to millions of people worldwide annually. Hence, the stability parameters of such suspensions, for example, sedimentation rate and the compactness of the formed sediments, are of great interest to achieve the most optimal and stable formulations. Unlike currently used analytical techniques involving visual observations and/or monitoring of several optical properties using specialized glassware, water proton nuclear magnetic resonance (wNMR) used in this work allows one to analyze samples in their original sealed container regardless of its opacity and/or labeling. It was demonstrated that the water proton transverse relaxation rate could be used to monitor in real time the sedimentation process of two widely used aluminum adjuvants—Alhydrogel® and Adju‐Phos®. Using wNMR, we obtained valuable information on the sedimentation rate, dynamics of the supernatant and sediment formation, and the sedimentation volume ratio (SVR) reflecting the compactness of the formed sediment. Results on SVR from wNMR were verified by caliper measurements. Verification of the sedimentation rate results from wNMR by other analytical techniques is challenging due to differences in the measured attributes and even units of the reported rate. Nonetheless, our results demonstrate the practical applicability of wNMR as an analytical tool to study pharmaceutical suspensions, for example, aluminum‐adjuvanted vaccines, to provide higher quality and more efficient vaccines. Such analyses could be carried out in the original container of a suspension drug product to study its colloidal stability and to monitor its quality over time without compromising product integrity.

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Section: Introductionmentioning

confidence: 99%

Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation

Taraban

2020

Magnetic Reson in Chemistry

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“…Aluminum adsorbed vaccines exposed to freezing temperatures lose their physical, chemical, and immunological properties and their administration can result not only in compromised immunogenicity but also increase adverse local reactions at an injection site, such as sterile abscesses [ 7 8 9 ]. Inadvertent vaccines’ freezing still happens often worldwide, although many efforts are being undertaken to prevent the patients from getting vaccinated with ineffective and unsafe products.…”

Section: Discussionmentioning

confidence: 99%

“…Sophisticated studies performed with the use of many different methods indicated significant physical and chemical differences between the freeze-damaged and non-frozen vaccine adjuvant and proved that the mechanisms of the frozen vaccine destruction are very complicated. They involve among others detachment of water from aluminum hydroxide hydrate particles that leads to the crushing of the viscous Alhydrogel structure [ 8 9 ]. The studies currently focus on resolving this problem aim at recognizing the mechanisms of frozen vaccines’ destruction and improvement of their temperature stability addition of compounds that stabilize aluminum adsorbed proteins in solutions, including osmolytes and cryoprotectants, such as glycine, propylene glycol, PEG 300, sucrose, and trehalose [ 21 22 23 24 25 26 27 28 ].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of precipitation time of the aluminum salts adsorbed potentially frozen vaccines used in the Polish National Immunization Schedule for their pre-qualification before the administration

Górska

Główka

Woźnica

et al. 2022

Clin Exp Vaccine Res

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Purpose Vaccines adsorbed on aluminum adjuvants irreversibly lose potency after freezing and their safety is affected. To prevent the administration of such vaccines, the World Health Organization developed the Shake Test designed to determine whether adsorbed vaccines have been frozen or not. However, the Shake Test is difficult and time-consuming when routinely conducted at the place of vaccination. In this study, a modified shake test for prequalification of potentially frozen vaccines was elaborated. Materials and Methods Vaccines used in the Polish Immunization Schedule were investigated and the analysis includes an assessment of precipitation time and the influence of the container type, amount and type of aluminum compound, and a volume of vaccine dose on the precipitation time. Results Significant differences between the precipitation time of frozen and non-frozen vaccines routinely used in the Polish Immunization Schedule were observed. The precipitation time of all non-frozen vaccines was above 30 minutes. The longest precipitation time of frozen vaccines was 10 minutes. Conclusion The finding of the study can be used in practice by the personnel administering vaccines to patients. Step-by-step recommendations for the preparation of the test have been proposed in the article.

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“…Aluminum-adjuvanted vaccines are temperature-sensitive formulations ( Chen et al., 2009 ; Clausi et al., 2008b ; Kurzatkowski et al., 2013 , 2018 ; Milstien et al., 2016 ). According to the recommendations by World Health Organization (WHO), aluminum-containing vaccines, e.g., diphtheria, hepatitis B, and polio, etc., should be transported and stored within a narrow temperature range at 2–8°C ( Organization, 2008 , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic elucidation of freezing-induced surface decomposition of aluminum oxyhydroxide adjuvant

Liang

et al. 2022

iScience

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Physical and chemical changes in Alhydrogel™ damaged by freezing

Cited by 15 publications

References 23 publications

Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation

Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation

Evaluation of precipitation time of the aluminum salts adsorbed potentially frozen vaccines used in the Polish National Immunization Schedule for their pre-qualification before the administration

Mechanistic elucidation of freezing-induced surface decomposition of aluminum oxyhydroxide adjuvant

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