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Preservative Induced Polysorbate 80 Micelle Aggregation
- Source :
- Journal of pharmaceutical sciences. 110(6)
- Publication Year :
- 2020
-
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.
- Subjects :
- Polysorbate
Preservative
Chemistry
Growth kinetics
Preservatives, Pharmaceutical
Pharmaceutical Science
Polysorbates
02 engineering and technology
Pharmaceutical formulation
021001 nanoscience & nanotechnology
030226 pharmacology & pharmacy
Small-angle neutron scattering
Micelle
Polyvinyl alcohol
Formulation stability
Excipients
03 medical and health sciences
chemistry.chemical_compound
Surface-Active Agents
0302 clinical medicine
Chemical engineering
0210 nano-technology
Micelles
Subjects
Details
- ISSN :
- 15206017
- Volume :
- 110
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of pharmaceutical sciences
- Accession number :
- edsair.doi.dedup.....904de3c649e0475bfe03c0de5b698e24