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Micelle formation and phase separation of poloxamer 188 and preservative molecules in aqueous solutions studied by small angle X-ray scattering

Published

Author(s)

Rachel Ford, Peter H. Gilbert, Roisin Donnelly, Richard E. Gillilan, Qingqiu Huang, Ken Qian, David Allen, Norman Wagner, Yun Liu

Abstract

Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can introduce aggregates and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution. A systematic study is conducted here to understand the phase behavior and morphological causes of aggregation of P188 in the presence of preservatives phenol and benzyl alcohol, primarily using small-angle x-ray scattering (SAXS). Based on SAXS results, P188 remains as unimers in solution when below a certain phenol concentration. Upon increasing the phenol concentration, a regime of micelle formation is observed due to the interaction between P188 and phenol. Further increasing the phenol concentration causes mixtures to become turbid and phase-separate over time. The effect of benzyl alcohol on the phase behavior is also investigated.
Citation
Journal of Pharmaceutical Sciences
Volume
112
Issue
3

Keywords

formulations, poloxamer 188, surfactant, micelle

Citation

Ford, R. , Gilbert, P. , Donnelly, R. , Gillilan, R. , Huang, Q. , Qian, K. , Allen, D. , Wagner, N. and Liu, Y. (2023), Micelle formation and phase separation of poloxamer 188 and preservative molecules in aqueous solutions studied by small angle X-ray scattering, Journal of Pharmaceutical Sciences, [online], https://doi.org/10.1016/j.xphs.2022.09.019, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=934633 (Accessed March 1, 2024)
Created March 1, 2023, Updated January 23, 2024