Radiosterilization of drugs in aqueous solutions may be achieved by the use of radioprotective excipients.
The aim of this study was to assess the feasibility of radiosterilization of drugs aqueous solutions and to evaluate the effects of some additives, such as mannitol, nicotinamide and pyridoxine, which might protect the drug from degradation. Metoclopramide was selected as a model drug. The structures of the degradation products were determined to gain insight on the radiolysis mechanisms in aqueous solution in order to design strategies to lower the drug degradation. Metoclopramide hydrochloride aqueous solutions with and without excipients were irradiated either with gamma rays or high-energy electrons. HPLC-DAD was used to measure the loss of chemical potency and to quantify the degradation products which were also characterized by LC-APCI-MS-MS. Metoclopramide recovery for gamma and electron beam-irradiated solutions containing either mannitol, pyridoxine or nicotinamide meets the pharmacopoeial specifications for metoclopramide content up to a 15 kGy irradiation so that metoclopramide solutions containing these excipients might be radiosterilized at 15 kGy either with gamma rays or high-energy electrons. Structures are proposed for the majority of radiolysis products. Similar radiolysis products were detected for gamma and electron beam irradiations but the chromatographic profiles were different (differences in the distribution of radiolysis products).
Maquille
Aubert
A
Laboratory of Chemical and Physico-chemical Analysis of Drugs (CHAM), Université Catholique de Louvain, Brussels, Belgium. aubert.maquille@cham.ucl.ac.be
Jiwan
Jean-Louis Habib
JL
Tilquin
Bernard
B
D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D003116:Color; D004583:Electrons; D005079:Excipients / Q000737:chemistry* / Q000528:radiation effects*; D005720:Gamma Rays; D008353:Mannitol / Q000737:chemistry / Q000528:radiation effects; D013058:Mass Spectrometry; D009536:Niacinamide / Q000737:chemistry / Q000528:radiation effects; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects*; D019999:Pharmaceutical Solutions; D011736:Pyridoxine / Q000737:chemistry / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000737:chemistry* / Q000528:radiation effects*; D011874:Radiometry; D013242:Sterilization / Q000379:methods*; D014867:Water
D005079:Excipients; D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D011837:Radiation-Protective Agents; D014867:Water; D009536:Niacinamide; D008353:Mannitol; D011736:Pyridoxine