Evidence map›Paper›PMID 29713822›Full record

ArticlePharmaceutical research2018

Improving Viscosity and Stability of a Highly Concentrated Monoclonal Antibody Solution with Concentrated Proline.

Jessica J Hung, Barton J Dear, Aileen K Dinin, Ameya U Borwankar, Sumarth K Mehta, Thomas T Truskett, Keith P Johnston

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
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  17. The Multifaceted Roles of Proline in Cell Behavior.Frontiers in cell and developmental biology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Jessica J HungMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Barton J DearMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Aileen K DininMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Ameya U BorwankarMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Sumarth K MehtaMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Thomas T TruskettMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Keith P JohnstonMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA. kpj@che.utexas.edu.
The University of Texas at Austin · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo explain the effects of the osmolyte proline on the protein-protein interactions (PPI), viscosity and stability of highly concentrated antibody solutions in contrast to other neutral osmolytes.

methodsThe viscosity of ~225 mg/mL mAb solutions was measured with proline, glycine and trehalose as a function of pH and co-solute concentration up to 1.3 M. The stability was assessed via turbidity as well as size exclusion chromatography after 4 weeks storage at 40°C. The PPI strength was assessed qualitatively via the high concentration diffusion rate by dynamic light scattering.

resultsIncreasing proline significantly reduced the mAb viscosity and increased the colloidal stability at pH 6, but not at pH 5 further from the mAb pI. In contrast, glycine and trehalose did not improve the viscosity nor stability. The normalized diffusion coefficient at high concentration, which is inversely proportional to the attractive PPI strength, increased with proline concentration but decreased with increasing glycine.

conclusionsProline demonstrated greater efficacy for improving mAb viscosity and stability in contrast to glycine and trehalose due to its amphipathic structure and partial charge on the pyrrolidine side chain. These properties likely allow proline to screen the attractive electrostatic and hydrophobic interactions that promote self-association and high viscosities. Binary proline-histidine formulations also demonstrated greater viscosity reduction effects than histidine alone at the same total co-solute concentration, while maintaining a lower total solution osmolarity.

Indexed as

Antibodies, MonoclonalChemistry, PharmaceuticalDrug StabilityPharmaceutical SolutionsProlineViscosityAntibodies, MonoclonalPharmaceutical SolutionsProlineantibodyhigh-concentrationprolinestabilityviscosity

Identifiers

PMID29713822
OpenAlexW2802582474

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.