Caffeine as a Viscosity Reducer for Highly Concentrated Monoclonal Antibody Solutions.

Autor:	Zeng Y; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States. Electronic address: yzeng@reformbiologics.com., Tran T; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States., Wuthrich P; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States., Naik S; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States., Davagnino J; KBI Biopharma Inc., 1101 Hamlin Rd, Durham, NC 27704, United States., Greene DG; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States., Mahoney RP; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States., Soane DS; ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2021 Nov; Vol. 110 (11), pp. 3594-3604. Date of Electronic Publication: 2021 Jun 26.
DOI:	10.1016/j.xphs.2021.06.030
Abstrakt:	Many monoclonal antibody (mAb) solutions exhibit high viscosity at elevated concentrations, which prevents manufacturing and injecting of concentrated mAb drug products at the small volumes needed for subcutaneous (SC) administration. Addition of excipients that interrupt intermolecular interactions is a common approach to reduce viscosity of high concentration mAb formulations. However, in some cases widely used excipients can fail to lower viscosity. Here, using infliximab and ipilimumab as model proteins, we show that caffeine effectively lowers the viscosity of both mAb formulations, whereas other common viscosity-reducing excipients, sodium chloride and arginine, do not. Furthermore, stability studies under accelerated conditions show that caffeine has no impact on stability of lyophilized infliximab or liquid ipilimumab formulations. In addition, presence of caffeine in the formulations does not affect in vitro bioactivities of infliximab or ipilimumab. Results from this study suggest that caffeine could be a useful viscosity reducing agent that complements other traditional excipients and provides viscosity reduction to a wider range of mAb drug products. (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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