Reduced Subvisible Particle Formation in Lyophilized Intravenous Immunoglobulin Formulations Containing Polysorbate 20

Zhou, Chen; Wei, Qi; Lewis, E. Neil; Randolph, Theodore W.; Carpenter, John F.

doi:10.1016/j.xphs.2016.05.013

Cited by 14 publications

(2 citation statements)

References 38 publications

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“…John F. Carpenter and Theodore W. Randolph have been pioneers in recognizing the importance of this problem. [9][10][11] Starting from a first publication on the lyophilization of hemoglobin in 1996, 12 their work has tremendously contributed to the understanding of the sources and mechanisms of protein aggregation during production, 13 formulation, 14,15 shipment and storage, 16,17 as well as handling by medical personnel and patients. 5,18 Together with advances in experimental characterization, this progress led to a fundamental understanding of the aggregation process at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

Accelerated Aggregation Studies of Monoclonal Antibodies: Considerations for Storage Stability

Wälchli

Vermeire

Massant

et al. 2020

Journal of Pharmaceutical Sciences

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Aggregation of mAbs is a crucial concern with respect to their safety and efficacy. Among the various properties of protein aggregates, it is emerging that their size can potentially impact their immunogenicity. Therefore, stability studies of antibody formulations should not only evaluate the rate of monomer loss but also determine the size distribution of the protein aggregates, which in turn depends on the aggregation mechanism. Here, we study the aggregation behavior of different formulations of 2 monoclonal immunoglobulins (IgGs) in the temperature range from 5 C to 50 C over 52 weeks of storage. We show that the aggregation kinetics of both antibodies follow non-Arrhenius behavior and that the aggregation mechanisms change between 40 C and 5 C, leading to different types of aggregates. Specifically, for a given monomer conversion, dimer formation dominates at low temperatures, while larger aggregates are formed at higher temperatures. We further show that the stability ranking of different molecules as well as of different formulations is drastically different at 40 C and 5 C while it correlates better between 30 C and 5 C. Our findings have implications for the level of information provided by accelerated aggregation studies with respect to protein stability under storage conditions.

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Section: Introductionmentioning

confidence: 99%

Accelerated Aggregation Studies of Monoclonal Antibodies: Considerations for Storage Stability

Wälchli

Vermeire

Massant

et al. 2020

Journal of Pharmaceutical Sciences

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“…Polysorbate, a substance prepared by the reaction of sorbitan fatty acid ester (a nonionic surfactant) with ethylene oxide. Polysorbates ("tweens") are widely used in industry and medicine as antistatic agents, defoamers, emulsifiers and solubilizers, fiber softeners, dispersing agent and substance that contributes to the dissolution of both water-soluble in the fat phase and waxes in the pharmaceuticals, and fat-soluble in the aqueous phase, in animal feed and soil treatment [115][116][117][118].…”

Section: Sorbitan Esters Of Fatty Acidsmentioning

confidence: 99%

Structure and Applications of Surfactants

Khalfallah

2024

Surfactants - Fundamental Concepts and Emerging Perspectives

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Surfactant molecules have two parts, a lipophilic (apolar) part that retains fat and a hydrophilic (polar) part that is miscible with water. The lipophilic portion consists of one or more aliphatic, straight or branched or aromatic or even alkylaromatic hydro- or fluorocarbon chains. The hydrophilic portion or polar head consists of one or more polar groups, ionic or nonionic. Surfactants have a wide variety of applications that include membrane permeabilization and dissolution, inclusion body solubilization, as well as membrane protein solubilization, biochemistry, crystallization, and manipulation. The behavior of these molecules is directly related to the aversion to water of the nonpolar groups, whereas the polar moieties tend to be highly hydrated. Their surfactant properties are therefore essentially based on the balance between the hydrophilic and hydrophobic parts of the molecule, called HLB (Hydrophile-Lipophile Balance).

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