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Preservative Induced Polysorbate 80 Micelle Aggregation.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 2021 Jun; Vol. 110 (6), pp. 2395-2404. Date of Electronic Publication: 2020 Dec 30. - Publication Year :
- 2021
-
Abstract
- Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that aggregation kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. Aggregation is a two-step process, where initial formation of small aggregates is followed by a period of monotonic power-law growth, providing evidence for the mechanism. Total aggregate mass stays constant after initial aggregate formation, and addition of a pH-regulating citrate buffer dramatically accelerates aggregation kinetics.<br /> (Copyright © 2020 American Pharmacists Association®. All rights reserved.)
- Subjects :
- Excipients
Preservatives, Pharmaceutical
Surface-Active Agents
Micelles
Polysorbates
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6017
- Volume :
- 110
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33387597
- Full Text :
- https://doi.org/10.1016/j.xphs.2020.12.030