1: Int J Pharm. 2007 Oct 1;343(1-2):4-11. Epub 2007 Apr 24.

Irradiation of human insulin in aqueous solution, first step towards
radiosterilization.

Terryn H, Maquille A, Houée-Levin C, Tilquin B.

Laboratory of Chemical and Physicochemical Analysis of Drugs (CHAM), Université
Catholique de Louvain, Brussels, Belgium.

The degradation of irradiated human insulin in aqueous solutions was investigated
in order to protect the protein against ionizing radiation. The influence of the 
drug concentration, excipients and irradiation temperature were studied. Aqueous 
solutions at pH 2 were irradiated by gamma rays or by accelerated electrons. Two 
different high-performance liquid chromatography (HPLC) methods were used:
reverse-phase high-performance liquid chromatography (RP-HPLC)/UV and size
exclusion liquid chromatography (SEC/UV) to investigate both the fragmentation
and the formation of higher molecular weight proteins. In solution without
excipients irradiated at ambient temperature at 10 kGy, the loss of human insulin
is almost complete. Addition of radio-protecting excipients (free radicals
scavengers) and cryo-irradiation allowed to decrease insulin degradation. The
best radio-protector used was ascorbic acid in aqueous solution and oxidized
glutathione in the frozen solutions. Only the combination of these two approaches
(addition of scavenger and freezing) enables the irradiated human insulin in
aqueous solution to meet the European Pharmacopoeia requirements for chemical
potency (>or=90%).

PMID: 17537599 [PubMed - in process]

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