Simulated space radiation: Investigating ionizing radiation effects on the stability of amlodipine besylate API and tablets

Abstract

Efficacious pharmaceuticals with the adequate shelf life are essential for the well-being of the space explorers and successful completion of a space mission. Space is brimming with different types of radiations, which penetrate inside the spacecraft despite the shielding material. Such radiations can alter the stability of the pharmaceuticals during long duration space missions. The literature reporting the space radiation effects on the pharmaceuticals is scarce in a public domain. Ground-based simulation studies can be useful to predict the influence of the space radiations on the stability of the pharmaceuticals. Based upon these facts, the main objective of the present preliminary work was to investigate the effect of different types of ionizing radiations on the stability of amlodipine besylate API and tablets. Amlodipine besylate samples were irradiated by protons, neutrons (thermal and fast), gamma and heavy ion (56Fe) radiations with their different doses. The samples were also irradiated with UV–visible radiation to compare the effect of selected ionizing radiations with photodegradation. The physical stability was examined through organoleptic evaluation and the chemical stability was evaluated by FTIR and HPLC. The results of the organoleptic evaluation showed colour changes from colourless to yellow in proton irradiated solid API and gamma irradiated API aqueous solution. The FTIR spectrum of proton irradiated API showed one additional absorption band at 1728 cm−1 due to degradation products. HPLC analysis revealed that amlodipine degraded up to 10% and 21% after the highest doses of proton and gamma irradiation, respectively. No physical or chemical changes were observed after neutron and 56Fe irradiation. The structures of major radiolytic products were elucidated using LC-MS/MS. Two new impurities were found in the API aqueous solution as a result of gamma irradiation. The drug degradation pathways were postulated by proposing the plausible mechanism of formation.