Application of EPR Spectroscopy for Examination of Free Radical Formation in Thermally Sterilized Betamethasone, Clobetasol, and Dexamethasone

Abstract

Paramagnetic centers in the three glucocorticosteroid drugs, such as betamethasone, clobetasol, and dexamethasone, were examined by the use of X-band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. Glucocorticosteroid drugs were sterilized according to the norms at 160°C (120 min), 170°C (60 min), and 180°C (30 min). Free radical properties, types, and concentrations in the individual glucocorticosteroids were compared. The lineshape and parameters of EPR curves recorded in the range of the microwave power of 0.7-70 mW were tested. The non-heated drugs were diamagnetic. Free radicals were formed in clobetasol and dexamethasone drugs during process of their thermal sterilization, while free radicals were not detected in thermally sterilized betamethasone. Fast spin-lattice relaxation processes existed in heated clobetasol and dexamethasone. Their EPR lines were homogeneously broadened. A complex free radical system characterized these two drugs. Optimal conditions of sterilization of glucocorticosteroids were obtained. Betamethasone may be sterilized at 160, 170, and 180°C. Clobetasol may be sterilized at 160 and 170°C. Dexamethasone may be sterilized at 170 and 180°C.

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

“…The following parameters of EPR spectra: -factor,amplitude, -integral intensity, and linewidth (Δ pp ), were determined as was described elsewhere [6][7][8][10][11][12].…”

“…The integral intensities of the EPR lines of examined steroids ( ) and ultramarine ( ) were calculated by double integration of the first-derivative EPR spectra. Free radical concentrations ( ) in the studied samples were determined based on the proportional relationship with integral intensity of the EPR lines [6][7][8][10][11][12]. Sample integral intensities in EPR spectra were examined and compared with an ultramarine reference.…”

“…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.…”

“…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].…”