Influence of ionising irradiation on clotrimazole in the solid state.

The effect of ionising irradiation on the antifungal drug clotrimazole has been studied. The compound was subjected to ionisation irradiation in the form of high-energy electron beam (25-800 kGy) from an accelerator. Before and after the irradiation the compound was subjected to the EPR, TLC, HPLC and HPLC-MS analysis. After irradiation with doses 400-800 kGy the colour of the substance was changed from white to cream. Four products of radiolysis appeared in the HPLC chromatogram at 7.7, 4.2, 6.4 and 14.6 min and the active ingredient content decreased to 96.5%. The irradiation with a dose of 25 kGy resulted in the appearance of trace amounts of the product at 7.7 min and free radicals (2.54 x 10(14)spins/g). On the basis of the HPLC-MS data, the main product of radiolysis (t(R)=7.7 min) is 1-(9-phenylfluoren-9-yl)-imidazole. Besides traces of (2-chlorophenyl)-diphenylmethanol, other impurities listed in the European Pharmacopoeia (European Pharmacopea, 5th edition, Council of Europe, Strasbourg, France, 2004.) have not been detected. Clotrimazole has been found to show relatively high resistance to ionising irradiation (greater than fluconazole) and probably will be suitable for radiation sterilisation but with doses lower than 25 kGy.

The influence of radiation sterilization on thiamphenicol.

The effect of ionising radiation, applied in the form of an electron beam, in the doses of 25, 100 and 400 kGy on the physical and chemical properties of thiamphenicol in solid phase has been studied by organoleptic analysis (form, colour, smell, solubility, clarity) and spectroscopic methods (UV, IR, EPR), chromatography (TLC), SEM observations, X-ray diffraction, polarimetry and thermal method (DSC). The above-discussed results have proved that on irradiation with a dose of 25 kGy no significant changes appear in thiamphenicol, apart from the formation of free radicals of the lifetime of over 352 days. On irradiation with much higher doses (100 and 400 kGy) no changes were observed in the IR spectra but the UV line intensities slightly increased at lambda(max)=266 and 273 nm, the colour of the powder changed, the radiolysis products appeared as detected by TLC, changes were also observed in the XRD, SEM pictures, the melting point values (DSC) and optical rotation. On the basis of DSC results a linear relation was found between the irradiation dose and the decrease in the melting point and increase in the enthalpy of melting, characterised by high correlation coefficients of r=0.9839 and 0.9622, respectively. Moreover, a linear relation was established between the optical rotation angle and the irradiation dose, alpha(D) ( degrees )=f(dose), characterised by the correlation coefficient r=0.9874. The results obtained indicate that thiamphenicol can be safely subjected to radiation sterilization by the standard dose of 25 kGy.