The Interface Motion and Hydrodynamic Shear of the Liquid Slosh in Syringes

Zhang, Yuchen; Han, Dingding; Dou, Zhongwang; Veilleux, Jean-Christophe; Shi, Galen; Collins, D. M.; Vlachos, Pavlos P.; Ardekani, Arezoo M.

doi:10.1007/s11095-021-02992-3

Cited by 9 publications

(6 citation statements)

References 35 publications

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“…The pressure gradients arising in the solution when the bag comes to an abrupt stop can cause air from the bag head space to be forced into the solution, with air bubble entrainment and resulting foaming. Analogously, experiments with prefilled syringes in spring-driven autoinjectors show that upon actuation the spring pushes the plunger so hard that the air gap is compressed and pressurized, and air is forced into the solution [126][127][128][129] . As result there can be high levels of bubbles forming in the solution after the mechanical force is dissipated.…”

Section: Potential Mechanisms For Protein Particle Formation During Pts Transportation Of IV Bagsmentioning

confidence: 99%

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Linkuvienė

Ross

Crawford

et al. 2022

Journal of Pharmaceutical Sciences

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Potential Mechanisms For Protein Particle Formation During Pts Transportation Of IV Bagsmentioning

confidence: 99%

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Linkuvienė

Ross

Crawford

et al. 2022

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

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“…Instead, they generally rely on physicochemical properties of both the protein and solution such as diffusivities, surface tension, and various free-energies and kinetic rate constants, while molecular aspects such as protein–protein and protein-solvent/excipient interactions are often treated in a mean-field approximation. 92–94 This relative simplicity of the continuum models facilitates studying the behavior of protein solutions with significantly less computational resources than molecular models.…”

Section: Types Of Protein Modelsmentioning

confidence: 99%

“…Among the different types of continuum models, those based in computational fluid dynamics (CFD) are arguably the most broadly used in the pharmaceutical industry, with various applications to different stages of upstream and downstream process development. 95–97 The success of CFD to study problems involving fluid flows has led to the development of a number of different models for studying the behavior of concentrated protein solutions under mechanical stresses such as shear forces in pre-filled syringes 92 , 98 and dense environments like subcutaneous tissue. 99 Similarly, several mechanistic kinetic models for protein aggregation have been developed to assess and predict the effect of different formulation parameters (e.g., pH, ionic strength, temperature) on the nucleation and growth of high molecular weight species.…”

Section: Types Of Protein Modelsmentioning

confidence: 99%

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Blanco

2022

mAbs

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Computational prediction of the behavior of concentrated protein solutions is particularly advantageous in early development stages of biotherapeutics when material availability is limited and a large set of formulation conditions needs to be explored. This review provides an overview of the different computational paradigms that have been successfully used in modeling undesirable physical behaviors of protein solutions with a particular emphasis on high-concentration drug formulations. This includes models ranging from all-atom simulations, coarse-grained representations to macro-scale mathematical descriptions used to study physical instability phenomena of protein solutions such as aggregation, elevated viscosity, and phase separation. These models are compared and summarized in the context of the physical processes and their underlying assumptions and limitations. A detailed analysis is also given for identifying protein interaction processes that are explicitly or implicitly considered in the different modeling approaches and particularly their relations to various formulation parameters. Lastly, many of the shortcomings of existing computational models are discussed, providing perspectives and possible directions toward an efficient computational framework for designing effective protein formulations.

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“…However, the velocity used to advect the phase field in [22,23,25] is not guaranteed to be solenoidal, and needs to be modified to maintain energy-stability. A simplifying assumption made in [22,23,25] was to use a constant coefficient Pressure Poisson equation 3 . This is an elegant simplification, particularly for cases where the system behavior is not very sensitive to the density ratio 4 .…”

Section: Second-order Energy-stable Scheme Projection Schemementioning

confidence: 99%

“…Capturing the interfacial dynamics is crucial for gaining fundamental understanding of twophase flows. In several applications like bio-microfluidics and advanced manufacturing such interface resolved simulations are critical for analysis and design [1][2][3]. More generally, the availability of robust and fast interface-resolved two-phase simulations can greatly enable the development of (data-driven) coarse-scale models that need not be interface-resolving.…”

Section: Introductionmentioning

confidence: 99%

A projection-based, semi-implicit time-stepping approach for the Cahn-Hilliard Navier-Stokes equations on adaptive octree meshes

Khanwale,

Saurabh,

Ishii

et al. 2021

Preprint

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We present a projection-based framework for solving a thermodynamically-consistent Cahn-Hilliard Navier-Stokes system that models two-phase flows. In this work we extend the fully implicit method presented in Khanwale et al. [A fully-coupled framework for solving Cahn-Hilliard Navier-Stokes equations: Second-order, energy-stable numerical methods on adaptive octree based meshes., arXiv:2009.06628 (2020)], to a block iterative hybrid method. We use a projection-based semi-implicit time discretization for the Navier-Stokes and a fully-implicit time discretization for the Cahn-Hilliard equation. We use a conforming continuous Galerkin (cG) finite element method in space equipped with a residual-based variational multiscale (RBVMS) formulation. Pressure is decoupled using a projection step, which results in two linear positive semi-definite systems for velocity and pressure, instead of the saddle point system of a pressure-stabilized method. All the linear systems are solved using an efficient and scalable algebraic multigrid (AMG) method. We deploy this approach on a massively parallel numerical implementation using parallel octree-based adaptive meshes. The overall approach allows the use of relatively large time steps with much faster time-to-solve. We present comprehensive numerical experiments showing detailed comparisons with results from the literature for canonical cases, including the single bubble rise and Rayleigh-Taylor instability.

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The Interface Motion and Hydrodynamic Shear of the Liquid Slosh in Syringes

Cited by 9 publications

References 35 publications

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

A projection-based, semi-implicit time-stepping approach for the Cahn-Hilliard Navier-Stokes equations on adaptive octree meshes

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