Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions
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Author(s)
Awanish Kumar, Fnu
Klibanov, Alexander M
Date Issued
January 2017
Journal
Applied Biochemistry and Biotechnology
Publisher
Springer US
Citation
Kumar, Awanish, and Alexander M. Klibanov. “Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions.” Applied Biochemistry and Biotechnology, vol. 182, no. 4, Aug. 2017, pp. 1491–96.
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Author's final manuscript
Abstract
The problem of gelation of concentrated protein solutions, which poses challenges for both downstream protein processing and liquid formulations of pharmaceutical proteins, is addressed herein by employing previously discovered viscosity-lowering bulky salts. Procainamide-HCl and the salt of camphor-10-sulfonic acid with l-arginine (CSA-Arg) greatly retard gelation upon heating and subsequent cooling of the model proteins gelatin and casein in water: Whereas in the absence of additives the proteins form aqueous gels within several hours at room temperature, procainamide-HCl for both proteins and also CSA-Arg for casein prevent gel formation for months under the same conditions. The inhibition of gelation by CSA-Arg stems exclusively from the CSA moiety: CSA-Na was as effective as CSA-Arg, while Arg-HCl was marginally or not effective. The tested bulky salts did not inhibit (and indeed accelerated) temperature-induced gel formation in aqueous solutions of all examined carbohydrates―starch, agarose, alginate, gellan gum, and carrageenan. Keywords: Carbohydrates, Downstream processing of biologics, Gel formation, Hydrophobic salts, Intermolecular interactions in solution, Proteins
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1007/s12010-017-2413-8
