Table II

Summary of Solid Pharmaceuticals Evaluated for Radical Production by Electron Paramagnetic Resonance (EPR)

Investigation MethodsSubstancesIndicationRadiation ConditionsObservations
EPR (49)AminoglutethimideAnti-steroidMicrocrystalline powder form, 10 and 20 kGy at 5 kGy/h with EPR 4/8 wks after irradiation

  • Report confirmed and quantified the presence of longer-lived free radicals trapped in the microcrystalline lattice of the powder drugs

  • Most significant groups that increase radical concentrations are P=O(O), carboxyl-, ester-, or sulphur-containing substituents

  • Extensive characterization of the radical type from interpretation of the EPR spectra

  • Important note was that free radicals generated in the solid state would not be preserved in solution (i.e., in the instances with carbon-, oxygen-, or sulphur-centered radicals)

AzathioprineImmunosuppressive
ClozapineAntipsychotic
FlutamideNon-steroidal antiandrogen
IfosfamideChemotherapy
IndobufenPlatelet aggregation inhibitor
KetoconazoleAntifungal
MercaptopurineImmunosuppressive
MesalazineAnti-inflammatory
MetronidazoleAntibiotic
NifedipineCalcium channel blocker
NimodipineCalcium channel blocker
NitrendipineCalcium channel blocker
OrnidazoleAntiamoebic
Tamoxifen CitrateEstrogen receptor antagonist
EPR (50)CilazaprilACE Inhibitor1–20 kGy, EPR measurement performed several times over 2 years

  • No EPR spectra were observed for the non-irradiated drugs

  • Gamma irradiation produced stable alkyl- and amine-type free radicals

Diltiazem HClHypertension
Doxazosin Mesylateα1-Selective alpha blocker
Enalapril MaleateACE Inhibitor
LisinoprilACE Inhibitor
PentoxifyllineIntermittent claudication
Pergolide MesylateDopamine receptor agonist
SelegilineParkinson's Disease
Sodium ValproateAnticonvulsant
EPR (51)FelodipineCalcium channel blockerPowders irradiated at room temperature to 20 kGy dose at 1.02 Gy/h, EPR evaluated with stability samples (9 months)

  • Study evaluated the formation and longevity of radicals

  • EPR spectra for all compounds showed qualitatively identical EPR spectral features in terms of G-values

  • Radicals generated are very stable, surviving long periods of time in excess of 9 months

  • Residual radical population is high enough to be detectable after long storage

Nifedipine
Nimodipine
Nitrendipine