1. Eur J Pharm Biopharm. 2008 May;69(1):358-63. Epub 2007 Nov 23.

Cryo-irradiation as a terminal method for the sterilization of drug aqueous
solutions.

Maquille A, Habib Jiwan JL, Tilquin B.

Laboratory of Chemical and Physico-chemical Analysis of Drugs (CHAM), Université 
Catholique de Louvain, Brussels, Belgium. aubert.maquille@cham.ucl.ac.be
<aubert.maquille@cham.ucl.ac.be>

The aim of this study is to evaluate the specificities of the irradiation of
drugs in frozen aqueous solution. The structures of the degradation products were
determined to gain insight into the radiolysis mechanisms occurring in frozen
aqueous solutions. Metoclopramide hydrochloride and metoprolol tartrate were
chosen as models. The frozen solutions were irradiated at dry ice temperature by 
high energy electrons at various doses. The drug purity (chemical potency) and
the radiolysis products were quantified by HPLC-DAD. Characterization of the
degradation products was performed by LC-APCI-MS-MS. The structures of the
radiolysis products detected in irradiated frozen aqueous solutions were compared
to those detected in solid-state and aqueous solutions (previous studies). For
both metoclopramide and metoprolol, solute loss upon irradiation of frozen
aqueous solutions was negligible. Five radiolysis products present in traces were
identified in irradiated metoclopramide frozen solutions. Three of them were
previously identified in solid-state irradiated metoclopramide crystals. The two 
others were formed following reactions with the hydroxyl radical (indirect
effect). Only one fragmentation product was observed in irradiated metoprolol
frozen solutions. For both drugs, radiosterilization of frozen solutions, even at
high doses (25 kGy), was found to be possible.

PMID: 18248804 [PubMed - indexed for MEDLINE]