Radiation Sterilization of Anthracycline Antibiotics in Solid State

Abstract

The impact of ionizing radiation generated by a beam of electrons of 25–400 kGy on the stability of such analogs of anthracycline antibiotics as daunorubicin (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR results, it was established that unstable free radicals decay exponentially with the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation. Radiation-induced structural changes were analyzed with the use of spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM). A chromatographic method (HPLC-DAD) was applied to assess changes in the contents of the analogs in the presence of their impurities. The study showed that the structures of the analogs did not demonstrate any significant alterations at the end of the period necessary for the elimination of unstable free radicals. The separation of main substances and related substances (impurities and potential degradation products) allowed determining that no statistically significant changes in the content of particular active substances occurred and that their conversion due to the presence of free radicals resulting from exposure to an irradiation of 25 kGy (prescribed to ensure sterility) was not observed.

Antimicrobial Activity and Stability of Electron Beam Irradiated Dental Irrigants

“…The findings of the present study are in accordance with the published report which illustrated no change in the pH of irradiated sulphonamide [20]. However, the earlier study demonstrated the formation of free radicals by analogs of anthracycline followed by e-beam irradiation at 25 kGy [21]. Further, the complex-free radicals formed following the gamma irradiation of penicillin derived antibiotics at 25 kGy were decreased with storage time of 80 d [22].…”

Effect of UV Irradiation and Temperature on Free Radical Properties in Dehydrocholic and Ursodeoxycholic Acids: An EPR Study

“…Electron paramagnetic resonance (EPR) spectroscopy is a known electromagnetic technique used for recording paramagnetic centers, such as free radicals [1][2][3][4][5]. Thus, it has application in different research fields like medicine and pharmacy, for example, to characterize the mechanism of pharmacological action of drugs or to estimate the effect of radiation on drug delivery system and also on its stability in solid state and in aqueous solutions, respectively [1,[6][7][8][9][10][11][12][13]. Recently, the current literature review proves various applications of EPR spectroscopy in pharmacy, for example, to examine the stability of UV irradiated and thermally sterilized drugs, especially antibiotics [6,13] and glucocorticosteroids [7].…”

“…Thus, it has application in different research fields like medicine and pharmacy, for example, to characterize the mechanism of pharmacological action of drugs or to estimate the effect of radiation on drug delivery system and also on its stability in solid state and in aqueous solutions, respectively [1,[6][7][8][9][10][11][12][13]. Recently, the current literature review proves various applications of EPR spectroscopy in pharmacy, for example, to examine the stability of UV irradiated and thermally sterilized drugs, especially antibiotics [6,13] and glucocorticosteroids [7]. Because the sterilized antibiotics, especially coming from anthracycline family, such as doxorubicin, daunorubicin, epidoxorubicin, are widely applied in anticancer therapy (e.g., in leukemia and breast cancer) [13], there is a need to examine their vulnerability to thermal and UV irradiation prior use.…”

“…Recently, the current literature review proves various applications of EPR spectroscopy in pharmacy, for example, to examine the stability of UV irradiated and thermally sterilized drugs, especially antibiotics [6,13] and glucocorticosteroids [7]. Because the sterilized antibiotics, especially coming from anthracycline family, such as doxorubicin, daunorubicin, epidoxorubicin, are widely applied in anticancer therapy (e.g., in leukemia and breast cancer) [13], there is a need to examine their vulnerability to thermal and UV irradiation prior use. Similar requirements should be fulfilled in the case of steroid drugs which belong to the most important anti-inflammatory, antiallergic, and immunosuppressive agents, used in dermatology and ophthalmology in form of sterile pharmaceutical formulations, like, for example, prednisolone [7,14].…”

Hydrophilic Polyhedral Oligomeric Silsesquioxane, POSS(OH)32, as a Complexing Nanocarrier for Doxorubicin and Daunorubicin

“…The We used FTIR to study the structural characteristics of the DOX/DAU:POSS complexes in PBS (pH 7.4) after 24 h at 310 K ( Figure 3). The FTIR spectrum of DOX indicated the characteristic peaks at 3523 cm −1 (ν O-H ); 3321 cm −1 (ν O-H , ν N-H ); 2974, 2954, 2932 and 2896 cm −1 (ν O-H , aromatic ring), 1724 cm −1 (ν C=O , ketone); 1616 (sc, NH 2 ), 1580 cm −1 (ν C=C , aromatic ring); 1525 cm −1 (δ C-O-H , aromatic ring); 1413 cm −1 (δ O-C-H ; δ N-C-H ); 1283 cm −1 (ν C-O-H , aromatic ring); 1201 cm −1 (ν C-O , glycosidic bond); 1234 cm −1 (δ C-O-H , COCH 2 OH group) and 1205 cm −1 (δ CO-H , aromatic ring in DAU); and 1191 cm −1 (ν C-O , glycosidic bond in DAU) [20]. In contrast, the DOX:POSS spectrum indicated that peak intensities at 1525 cm −1 (δ C-O-H , aromatic ring), 1723 cm −1 (ν C=O , ketone), 1234 cm −1 (δ C-O-H , COCH 2 OH group), 1283 cm −1 (ν C-O-H , aromatic ring) and 1201 cm −1 (ν C-O , glycosidic bond) decreased.…”