An Electron Paramagnetic Resonance (EPR) spectroscopy study on the γ irradiation sterilization of the pharmaceutical excipient L histidine

regeneration of the radicals in solution

Claudio Vallotto, H. E. Williams, Damien Murphy, Zoe Ayres, Ruth Edge, Mark Newton, Christopher Wedge

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The effects of γ-radiation sterilization on the parenteral excipient L-histidine were analysed by means of EPR spectroscopy. The irradiation process was found to induce the formation of a deamination radical which was persistent in the solid state. The nature and reactivity of the radicals following dissolution in water was evaluated using spin-trapping EPR experiments. The deamination radical was found to regenerate in solution in the presence of trace metals, potentially leading to radical induced degradation reactions occurring up to an hour after the dissolution process. Understanding this process is significant for the improved design of parental pharmaceutical formulations in which unwanted radical reactions after γ‐radiation sterilization could lead to degradation of active ingredients.
Original languageEnglish
Pages (from-to)315-319
Number of pages5
JournalInternational Journal of Pharmaceutics
Volume533
Issue number1
Early online date28 Sep 2017
DOIs
Publication statusPublished - 25 Nov 2017
Externally publishedYes

Fingerprint

Deamination
Excipients
Electron Spin Resonance Spectroscopy
Histidine
Regeneration
Spectrum Analysis
Spin Trapping
Drug Compounding
Radiation Effects
Pharmaceutical Preparations
Metals
Radiation
Water

Cite this

@article{d3ec31e86c6b409b8a869e3b5506f503,
title = "An Electron Paramagnetic Resonance (EPR) spectroscopy study on the γ irradiation sterilization of the pharmaceutical excipient L histidine: regeneration of the radicals in solution",
abstract = "The effects of γ-radiation sterilization on the parenteral excipient L-histidine were analysed by means of EPR spectroscopy. The irradiation process was found to induce the formation of a deamination radical which was persistent in the solid state. The nature and reactivity of the radicals following dissolution in water was evaluated using spin-trapping EPR experiments. The deamination radical was found to regenerate in solution in the presence of trace metals, potentially leading to radical induced degradation reactions occurring up to an hour after the dissolution process. Understanding this process is significant for the improved design of parental pharmaceutical formulations in which unwanted radical reactions after γ‐radiation sterilization could lead to degradation of active ingredients.",
keywords = "Electron Paramagnetic Resonance (EPR), Spin-trapping, Sterilization, Irradiation, Dissolution, Fenton reaction",
author = "Claudio Vallotto and Williams, {H. E.} and Damien Murphy and Zoe Ayres and Ruth Edge and Mark Newton and Christopher Wedge",
year = "2017",
month = "11",
day = "25",
doi = "10.1016/j.ijpharm.2017.09.068",
language = "English",
volume = "533",
pages = "315--319",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1",

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An Electron Paramagnetic Resonance (EPR) spectroscopy study on the γ irradiation sterilization of the pharmaceutical excipient L histidine : regeneration of the radicals in solution. / Vallotto, Claudio; Williams, H. E.; Murphy, Damien; Ayres, Zoe; Edge, Ruth; Newton, Mark; Wedge, Christopher.

In: International Journal of Pharmaceutics, Vol. 533, No. 1, 25.11.2017, p. 315-319.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An Electron Paramagnetic Resonance (EPR) spectroscopy study on the γ irradiation sterilization of the pharmaceutical excipient L histidine

T2 - regeneration of the radicals in solution

AU - Vallotto, Claudio

AU - Williams, H. E.

AU - Murphy, Damien

AU - Ayres, Zoe

AU - Edge, Ruth

AU - Newton, Mark

AU - Wedge, Christopher

PY - 2017/11/25

Y1 - 2017/11/25

N2 - The effects of γ-radiation sterilization on the parenteral excipient L-histidine were analysed by means of EPR spectroscopy. The irradiation process was found to induce the formation of a deamination radical which was persistent in the solid state. The nature and reactivity of the radicals following dissolution in water was evaluated using spin-trapping EPR experiments. The deamination radical was found to regenerate in solution in the presence of trace metals, potentially leading to radical induced degradation reactions occurring up to an hour after the dissolution process. Understanding this process is significant for the improved design of parental pharmaceutical formulations in which unwanted radical reactions after γ‐radiation sterilization could lead to degradation of active ingredients.

AB - The effects of γ-radiation sterilization on the parenteral excipient L-histidine were analysed by means of EPR spectroscopy. The irradiation process was found to induce the formation of a deamination radical which was persistent in the solid state. The nature and reactivity of the radicals following dissolution in water was evaluated using spin-trapping EPR experiments. The deamination radical was found to regenerate in solution in the presence of trace metals, potentially leading to radical induced degradation reactions occurring up to an hour after the dissolution process. Understanding this process is significant for the improved design of parental pharmaceutical formulations in which unwanted radical reactions after γ‐radiation sterilization could lead to degradation of active ingredients.

KW - Electron Paramagnetic Resonance (EPR)

KW - Spin-trapping

KW - Sterilization

KW - Irradiation

KW - Dissolution

KW - Fenton reaction

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DO - 10.1016/j.ijpharm.2017.09.068

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JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

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