title: The influence of ionizing radiation on itraconazole in the solid state.
abstract: The aim of this study was to investigate the ionizing radiation effects, in the form of an electron beam, on itraconazole (ITR) in the solid phase. It was found that the ITR, under the influence of a standard 25 kGy dose of radiation used for the sterilization of drug substances, decomposed at 0.4%. Moreover, a gentle change of colour and a decrease in melting point does not exceed pharmacopoeial standards causing that ITR can be sterilized by radiation method. The use of high 400 kGy radiation doses resulted in a 6.5% decomposition of the ITR and eight radiodegradation products were found. However, with the exception of differential scanning calorimetry (DSC), the X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible (UV-vis) methods showed no changes in the form and the morphology of the crystals. The structures of all those compounds were investigated. It was confirmed that the ITR decomposition takes place by dehalogenation (one of Cl atom elimination), the oxidation in isobutyl residue (beside the triazole ring) and C-O bond rupture.
authors.affiliation: Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780, Poznań, Poland, dettlaff@ump.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dettlaff
authors.forename: Przemysław
authors.initials: P
authors.lastname: Talik
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Spólnik
authors.forename: Witold
authors.initials: W
authors.lastname: Danikiewicz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ogrodowczyk
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000528:radiation effects; D004355:Drug Stability; D004583:Electrons; D017964:Itraconazole / Q000737:chemistry* / Q000528:radiation effects*; D010316:Particle Size; D044367:Phase Transition; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D013242:Sterilization / Q000379:methods*; D044366:Transition Temperature / Q000528:radiation effects
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole