Electron Beam Radiation as a Safe Method for the Sterilization of Aceclofenac and Diclofenac—The Usefulness of EPR and 1H-NMR Methods in Determination of Molecular Structure and Dynamics

Abstract

Diclofenac (DC) [2-(2,6-Dichloroanilino)phenyl]acetic acid,) and aceclofenac (AC) 2-[2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxyacetic acid in substantia were subjected to ionizing radiation in the form of a beam of high-energy electrons from an accelerator in a standard sterilization dose of 25 kGy and higher radiation doses (50–400 kGy). We characterized non-irradiated and irradiated samples of DC and AC by using the following methods: organoleptic analysis (color, form), spectroscopic (IR, NMR, EPR), chromatographic (HPLC), and others (microscopic analysis, capillary melting point measurement, differential scanning calorimetry (DSC)). It was found that a absorbed dose of 50 kGy causes a change in the color of AC and DC from white to cream-like, which deepens with increasing radiation dose. No significant changes in the FT-IR spectra were observed, while no additional peaks were observed in the chromatograms, indicating emerging radio-degradation products (25 kGy). The melting point determined by the capillary method was 153.0 °C for AC and 291.0 °C for DC. After irradiation with the dose of 25 kGy for AC, it did not change, for DC it decreased by 0.5 °C, while for the dose of 400 kGy it was 151.0 °C and 286.0 °C for AC and DC, respectively. Both NSAIDs exhibit high radiation stability for typical sterilization doses of 25–50 kGy and are likely to be sterilized with radiation at a dose of 25 kGy. The influence of irradiation on changes in molecular dynamics and structure has been observed by 1H-NMR and EPR studies. This study aimed to determine the radiation stability of DC and AC by spectrophotometric, thermal and chromatographic methods. A standard dose of irradiation (25 kGy) was used to confirm the possibility of using this dose to obtain a sterile form of both NSAIDs. Higher doses of radiation (50–400 kGy) have been performed to explain the changes in DC and AC after sterilization.

Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate

“…CMCS showed exothermic peak at 317 °C [ 36 ] which corresponds to the degradation of the polymer and AA showed an endothermic peak at 312.74 °C. The AA-CMCS conjugate showed an endothermic peak at 90.76 °C [ 37 ]. Span 60 showed two endothermic peaks at 57.76 °C and 402.25 °C [ 38 ].…”

How Does Radiation Affect Curcumin Raw Material?

“…Following irradiation with a dose of 30 kGy, only the content of 4-vinylguaiacol showed an increase, amounting to 15%. While ionizing radiation is advantageous for products sensitive to heat, leaving no chemical residues, it is crucial to note the tendency, recognized so far for various synthetic compounds, to undergo chemical instability when exposed to ionizing radiation [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The probability of chemical instability increases with a rise in the radiation dose, and it is important to consider that, concerning the elimination of fungi like Aspergillus flavus , the literature indicates that a considerably high dose, approximately 10 kGy, is adequate for complete eradication.…”

Structure and properties of the acellular porcine cornea irradiated with electron beam and its in‐situ implantation

“…High‐energy electrons form free radicals in the genetic material of bacteria, fungi, and viruses and affect their transcription 10 . It has been used to sterilize ultra‐fine porcine bladder matrix, 11 poly(methyl methacrylate), 12 diclofenac, and aclofenac 13 . Low doses of E‐beam radiation are used to sterilize biomaterials, such as human skin (18, 25, and 35 kGy), 14 donor cornea (15–21 kGy), 15 collagen scaffold (20 kGy), 11 and recombinant human type III collagen phosphorylated choline hydrogel (17, 19, or 21 kGy) 16 .…”

“…10 It has been used to sterilize ultra-fine porcine bladder matrix, 11 poly(methyl methacrylate), 12 diclofenac, and aclofenac. 13 Low doses of E-beam radiation are used to sterilize biomaterials, such as human skin (18, 25, and 35 kGy), 14 donor cornea (15-21 kGy), 15 collagen scaffold (20 kGy), 11 and recombinant human type III collagen phosphorylated choline hydrogel (17,19, or 21 kGy). 16 Medical devices are sterilized at doses of 15 or 25 kGy as described in ISO 11137.…”