Spectroscopic features of radiolytic intermediates induced in gamma irradiated sulfatiazole: an ESR study
Introduction
Gamma radiation has emerged as a useful, efficient and economic tool for sterilization of many drugs in their final containers, and it is more actively used now than at any time (Gopal, 1978, Bhalla et al., 1983, Jacobs, 1995, Reid, 1995). The advantages of sterilization by irradiation include high penetrating power, low chemical reactivity, low measurable residues, small temperature rise and the fact that there are fewer variables to control (Basly et al., 1996, Barbarin et al., 1999, Gibella et al., 2000). However, the adoption of this method requires detailed investigations to ensure that no undesirable changes take place, as ionizing radiation has been reported to cause degradation in the pharmaceuticals and therefore, creating reactive molecular fragments (Miyazaki et al., 1994, Schuler, 1994, Boess and Bögl, 1996), which may result in a toxicological hazard.
Electron spin resonance (ESR) technique appears to be well suited for determination of low concentration of free radicals in complex media and could permit the elucidation of mechanism of radiolysis even for a small radiation dose. Moreover, other features such as high sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques (Onori et al., 1996) to study radiolytic intermediates produced in irradiated solid samples. Previous results have already shown the suitability of ESR for the detection of irradiated drugs and foods (Bögl, 1989, Delincée, 1991, Desrosiers et al., 1991, Raffi et al., 1992, Raffi et al., 1994, Ciranni Signoretti et al., 1993, Ciranni Signoretti et al., 1994, Miyazaki et al., 1994, Raffi, 1998, Basly et al., 1999).
Although STZ is used in the sulfonamide containing drugs at a large extent, the applicability of the sterilization by radiation to the solid drugs containing STZ is not yet investigated in the literature. Therefore, the aims of the present work are: to characterize the radiolytic intermediates carrying unpaired electrons produced in gamma irradiated STZ in the dose range of 5–50 kGy and to explore the potential contribution of ESR technique in investigating the radiosterilization of STZ and/or drug delivery system containing STZ as active ingredient, through a detailed ESR study.
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Materials and methods
Sulfatiazole or with its chemical name, 4-amino-N-(thiazol-2-yl)benzenesulfonamide of spectroscopic grade was provided from Faculty of Pharmacy of Hacettepe University (Ankara) and was stored at room temperature in a well-closed container protected from light. No further purification was performed, and it was used as it was received. STZ is a white crystalline powder, which slowly darkens on exposure to light. The melting point of prismatic rods is about 200–204 °C while the other phase forms,
General features of the ESR spectra
Although unirradiated STZ exhibited no ESR signal, samples irradiated at room temperature showed a complex ESR spectrum consisting of 10 resonance peaks. Room temperature spectra recorded for two samples irradiated at two different radiation doses are given in Fig. 2a and b with the assigned peak numbers. The most intense resonance line appearing in the middle of the spectrum was found to have a g value of 2.0045 and a peak to peak width of 5.2 G. Increase in the absorbed dose caused more
Conclusions
Although unirradiated STZ exhibits no ESR signal, samples irradiated at room temperature exhibited a complex ESR spectra consisting of 10 resonance peaks, which saturated as inhomogenously brodened resonance lines in the microwave power range 1–80 mW.
Dose–response curves related with the studied resonance peaks follow exponential increases in the radiation dose range of 5–50 kGy.
Radical species responsible from experimental ESR spectra are unstable at normal (290 K open to air) and stability (313 K
Acknowledgments
We thank Professor Dr. Yekta Özer from Faculty of Pharmacy of Hacettepe University for providing kindly STZ samples of spectroscopic grade.
References (34)
- et al.
Role of residual solvents in the formation of volatile compounds after radiosterilization of cefotaxime
Int. J. Pharm.
(1999) - et al.
Gamma radiation induced effects on metronidazole
Int. J. Pharm.
(1996) - et al.
Radiation sterilization of polyethylene glycols
Int. J. Pharm.
(1983) Identification of irradiated foods-methods, development and concepts
Appl. Radiat. Isot.
(1989)- et al.
Appl. Radiat. Isot.
(1991) - et al.
ESR studies of some irradiated pharmaceuticals
Radiat. Phys. Chem.
(2000) Radiation sterilization of pharmaceuticals and polymers
Radiat. Phys. Chem.
(1978)- et al.
Electron Spin Resonance of Sulfite Radicals in Irradiated Calcite and Aragonite
Radiat. Phys. Chem.
(1992) - et al.
Temperature experiments on mollusk samples: an approach to ESR signal identification
Appl. Radiat. Isot.
(1989) - et al.
Estimation of irradiation dose of radiosterilized antibiotics by ESR: ampicillin
J. Pharm. Sci.
(1994)
ESR identification of irradiated antibiotics: Cephalosporins
Appl. Radiat. Isot.
Identifying Irradiated Foods
Trends Anal. Chem.
Three decades of spectroscopic studies of radiation produced intermediates
Radiat. Phys. Chem.
Basic ESR studies on recent corals
Q. Sci. Rev.
General properties of the paramagnetic center at g = 2.006 in carbonates
Quat. Sci. Rev.
Radiation induced effects on cephalosporins: an ESR study
Int. J. Radiat. Biol.
EPR and structure models for radical ions in anhydrite crystals
Fortschr. Mineral.
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