Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of pH, Ionic Strength, and Model Antigens

Muthurania, Kevin; Arunkumar, A.I.; Jin, Zhaowei; Williams, Jennifer; Ohtake, Satoshi

doi:10.1002/jps.24584

Cited by 21 publications

(15 citation statements)

References 28 publications

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“…After a certain preset time of sedimentation monitoring—most often 24 h—one also might measure the SVR as the ratio of the sediment height to the initial height of the suspension using the graduation markings on the Wintrobe tube. More precise information on the sedimentation process could be obtained using laser scattering analyzers [10] and optical scanner analyzers [8, 11] which provide simultaneous detection of light transmission and backscattering intensity to monitor sedimentation process and to obtain settling onset time, SR , and SVR. This technique also requires transferring the suspension to a specialized glass cuvette, typically with a sample volume of 20 mL [8].…”

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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“…The final vaccine suspension may switch between flocculated and deflocculated states, depending on the formulation conditions and the associated electrostatic interactions of the adjuvant particles. The sedimentation behavior of aluminum phosphate suspensions has been correlated to formulation parameters including pH, ionic strength, and the presence of model antigens ( Muthurania et al., 2015 ). The particles of aluminum with the immunogen can be reduced in size, resulting in a variation in the electrostatic interactions or flocculation behavior, morphology, and the surface properties (charge, viscosity, surface tension, etc.)…”

Section: Adjuvants For Carbohydrate-based Vaccinesmentioning

confidence: 99%

“…The particles of aluminum with the immunogen can be reduced in size, resulting in a variation in the electrostatic interactions or flocculation behavior, morphology, and the surface properties (charge, viscosity, surface tension, etc.) which may lead to a change of the visual characteristics of the product and to a different resuspension profile ( Hem and White, 1995 ; Maa and Hsu, 1996 ; Lindblad, 2004 ; Rowe et al., 2006 ; Muthurania et al., 2015 ; Kolade et al., 2015 ). It is important to measure all the physical parameters during the formulation process to determine optimal mixing conditions and the impact of shear on the aluminum particles.…”

Section: Adjuvants For Carbohydrate-based Vaccinesmentioning

confidence: 99%

Immunobiology of Carbohydrates: Implications for Novel Vaccine and Adjuvant Design Against Infectious Diseases

Stefanetti

Borriello

Richichi

et al. 2022

Front. Cell. Infect. Microbiol.

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Carbohydrates are ubiquitous molecules expressed on the surface of nearly all living cells, and their interaction with carbohydrate-binding proteins is critical to many immunobiological processes. Carbohydrates are utilized as antigens in many licensed vaccines against bacterial pathogens. More recently, they have also been considered as adjuvants. Interestingly, unlike other types of vaccines, adjuvants have improved immune response to carbohydrate-based vaccine in humans only in a few cases. Furthermore, despite the discovery of many new adjuvants in the last years, aluminum salts, when needed, remain the only authorized adjuvant for carbohydrate-based vaccines. In this review, we highlight historical and recent advances on the use of glycans either as vaccine antigens or adjuvants, and we review the use of currently available adjuvants to improve the efficacy of carbohydrate-based vaccines. A better understanding of the mechanism of carbohydrate interaction with innate and adaptive immune cells will benefit the design of a new generation of glycan-based vaccines and of immunomodulators to fight both longstanding and emerging diseases.

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“…Individual vaccines are already complex biological systems in itself, combination of the latter inevitably results into challenges regarding formulation and manufacture. For example, the pH and ionic strength may influence the binding of different antigens to the respective adjuvant . Another example is the decrease in the observed immunogenicity of inactivated poliovirus vaccines after combination with diphtheria‐tetanus‐whole‐cell‐pertussis vaccines containing the preservative thimerosal .…”

Section: General Considerations Requirements and Regulationsmentioning

confidence: 99%

“…During combination vaccine manufacture, the order of addition of components may impact the observed immunogenicity . As the facet of components and their pharmaceutical presentations is huge, the approaches tackling those challenges may differ tremendously depending on the kind of problem …”

Section: General Considerations Requirements and Regulationsmentioning

confidence: 99%

Challenges for the pharmaceutical technical development of protein coformulations

Mueller

Altenburger

Mohl

2017

Journal of Pharmacy and Pharmacology

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Objectives This review discusses challenges to stability, analytics and manufacturing of protein coformulations. Furthermore, general considerations to be taken into account for the pharmaceutical development of coformulated protein drug products are highlighted. Key findings Coformulation of two or more active substances in one single dosage form has recently seen increasing use offering several advantages, such as increased efficacy and/or the overall reduction of adverse event incidents in patients. Most marketed coformulated drug products are composed of small molecules. As proteins are not only comparatively large but also complex molecules, the maintenance of their physicochemical integrity within a formulation throughout pharmaceutical processing, storage, transport, handling and patient administration to ensure proper pharmacokinetics and pharmacodynamics in vivo already represents various challenges for single-entity products. Thus, nowadays, only sparse biologics-based coformulations can be found, as additional complexity during development is given for these products. Summary The complexity of the dosage form and the protein molecules results into additional challenges to formulation, manufacture, storage, transport, handling and patient administration, stability and analytics during the pharmaceutical development of protein coformulations. Various points have to be considered during different stages of development in order to obtain a safe and efficacious product.

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Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of pH, Ionic Strength, and Model Antigens

Cited by 21 publications

References 28 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

Immunobiology of Carbohydrates: Implications for Novel Vaccine and Adjuvant Design Against Infectious Diseases

Challenges for the pharmaceutical technical development of protein coformulations

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