Radiation sterilization of pharmaceuticals- chemical changes and consequences

Bögl, W.

doi:10.1016/0146-5724(85)90290-0

Cited by 25 publications

(11 citation statements)

References 5 publications

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“…The radiation sterilization and its impact on the properties of drugs have been described in the literature for almost 50 years. The first studies were focused on confirming the effectiveness and advantages of irradiation as a method of sterilization and establishing a standard dose for this process [ 1 , 2 , 3 , 4 , 5 , 6 ]. Whereas the majority of currently conducted research is aimed at verifying the possibility of using radiation for a specific type of drug-effect of this method on the physicochemical properties of the compound while maintaining an adequate level of the sterility [ 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Radiostability of Meropenem Trihydrate in Solid State

et al. 2018

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The influence of ionising radiation on the physicochemical properties of meropenem trihydrate in solid state was studied for doses of e-beam radiation: 25 kGy and 400 kGy. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile meropenem. No changes for meropenem irradiated with a dose of 25 kGy, the dose required to attain sterility, was confirmed in the results of spectroscopic (FT-IR), thermal (DSC, TGA) and X-ray powder diffraction (XRPD) studies. The radiation dose of 25 kGy produces no more than about 1500 ppm of radical defects. The chromatographic studies of irradiated meropenem in solutions did not show any chemical degradation. Moreover, the antimicrobial activity of meropenem irradiated with the dose of 25 kGy was unchanged. Based on the received results, we can conclude that radiostelization is a promising, alternative method for obtaining sterile meropenem. In the second part of the research, meropenem was exposed to e-beam radiation at the 400 kGy dose rate. It was confirmed, that reducing of antimicrobial activity could be connected with the degradation of β-lactam ring and changes in the trans-hydroxyethyl group. Apart from chemical changes, changes in the physical stability of irradiated meropenem (400 kGy) was also observed.

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Section: Introductionmentioning

confidence: 99%

The Radiostability of Meropenem Trihydrate in Solid State

et al. 2018

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“…The same irradiation dose using gamma radiation can be obtained in several hours, whereas electron beam radiation requires only a second [8]. The sterilisation procedures using irradiation have many advantages, such as high efficiency, no temperature requirements, possibility of sterilisation in packages but on the other hand, the ionisation radiation applied can damage a given drug being sterilised [9] so the effect of sterilisation radiation should be checked before its application. One of the most widely used methods of analysing the drugs purity and possible changes occurring during processing of drug is the differential scanning calorimetry (DSC) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

DSC and spectroscopic studies of disulfiram radiostability in the solid state

Marciniec

Dettlaff

Naskrent

et al. 2011

J Therm Anal Calorim

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The effect of ionising radiation on the physicochemical properties of disulfiram (Antabuse, Esperal, bisdiethylthiocarbamoil disulphide) has been studied by DSC, FTIR, EPR, MS, TLC and HPLC. Sterilisation was carried out in the solid state, at room temperature and normal air humidity using the electron beam of 9.96 Mev from accelerator. All the measurements were made simultaneously for the irradiated and nonirradiated substance. It has been found that the drug studied in solid phase when subjected to an electron beam corresponding to the irradiation in the doses 10-100 kGy shows the presence of free radicals (EPR), and a change in colour from white to pale green-grey that disappears after solution in water or methanol. After the irradiation with the dose of 100 kGy, its melting point and enthalpy slightly decreased. Also the content of the active substance decreases (HPLC-1.5%, UV-3.6%, iodometric titration method-2.7%) and trace amounts of the radiolysis products appear (HPLC). The substance irradiated with the doses 10-50 kGy does not show changes in the melting point, in the content and presence of the radiolysis products. The EPR results have shown that free radicals disappear after about a year and the discolouring disappears with them. The results of this study have shown that disulfiram can be subjected to sterilisation by irradiation with no deterioration of its physico-chemical properties, but a long time of storage needed to remove free radicals and discolouration questions the economic justification for this type of sterilisation.

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“…The factors causing the greatest damage during the irradiation process are radicals formed in the radiolysis reaction of water ( H 2 O · + , · OH , H 3 O + , H · , O · , H 2 , e − , e aq − ) ( 6 , 8 ). Therefore, the irradiation of therapeutic substances should be carried out in the solid state ( 6 , 7 , 9 ). Although the first studies on the sterilization of drugs are dated back to the 70s of the twentieth century (they concerned most often thermolabile antibiotics of the penicillin group), many of them has not known radiation resistance yet.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of radiodegradation is often different than the previously known mechanism either of photo- or thermodegradation. An assumption that the resistance of ionizing radiation is similar in the group of drugs with similar structure cannot be made ( 6 , 9 – 13 ). The comprehensive assessment for X-ray methods, spectroscopy, thermal and chromatographic analysis only enables capturing all changes that may occur during the irradiation process of a therapeutic compound, in order to ensure the safety of therapy ( 6 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

The Influence of Ionizing Radiation on Itraconazole in the Solid State

et al. 2014

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The aim of this study was to investigate the ionizing radiation effects, in the form of an electron beam, on itraconazole (ITR) in the solid phase. It was found that the ITR, under the influence of a standard 25 kGy dose of radiation used for the sterilization of drug substances, decomposed at 0.4%. Moreover, a gentle change of colour and a decrease in melting point does not exceed pharmacopoeial standards causing that ITR can be sterilized by radiation method. The use of high 400 kGy radiation doses resulted in a 6.5% decomposition of the ITR and eight radiodegradation products were found. However, with the exception of differential scanning calorimetry (DSC), the X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible (UV-vis) methods showed no changes in the form and the morphology of the crystals. The structures of all those compounds were investigated. It was confirmed that the ITR decomposition takes place by dehalogenation (one of Cl atom elimination), the oxidation in isobutyl residue (beside the triazole ring) and C-O bond rupture.

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Radiation sterilization of pharmaceuticals- chemical changes and consequences

Cited by 25 publications

References 5 publications

The Radiostability of Meropenem Trihydrate in Solid State

The Radiostability of Meropenem Trihydrate in Solid State

DSC and spectroscopic studies of disulfiram radiostability in the solid state

The Influence of Ionizing Radiation on Itraconazole in the Solid State

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