USING HIGH-CURRENT NANOSECOND LOW-ENERGY ELECTRON BEAMS FOR RADIATION STERILIZATION OF POWDERED DRUGS

Abstract

Modern technological schemes of manufacturing tabletized drugs usually eliminate microbiological contamination of processed and intermediate products. Therefore, sterility of the final drugs is determined by microbiological cleanness of the initial powdered materials. Powdered drug components cannot always be sterilized by even the most effective thermal method, because the parent drugs frequently possess insufficient thermal stability. Chemical sterilization by volatile agents (ethylene oxide, ozone) is also problematic because of the risk of toxin accumulation. Under these conditions an alternative is offered by the radiation sterilization process, since ionizing radiation is a universal damaging factor for microbiological flora of any kind (fungi, bacteria, spores, viruses), while a required sterilization dose of 25 – 50 kGy (irrespective of the radiation type) usually produces no detectable physicochemical changes in the irradiated material [1]. Radiation sterilization is usually produced using -radiation from isotope sources or high-energy (above 5 MeV) electron beams possessing considerable penetration ability in condensed matter. Construction of such radiation sources involves significant expenditures for the radiation protection of personnel. As a rule, special sterilization centers are built around such sources, where the final products are sterilized in a ready-to-use packed form [2, 3]. There is certain experience in using low-energy (150 – 500 keV) electron beams for sterilization purposes. The creation and use of such radiation sources requires neither capital investment for special buildings nor large expenditures for radiation protection. These systems can be arranged and operated immediately on enterprises. A disadvantage of such radiation sources is the relatively small penetration depth of low-energy electrons in solids (not exceeding 1.5 mm in water-equivalent materials). For this reason, use of these systems is restricted to surface sterilization, mostly of films, foils, paper, and related packaging materials [2 – 7]. Nevertheless, low-energy electron beams can ensure not only surface sterilization but bulk treatment as well, provided that the objects processed admit leveling of the irradiation in depth by means of intense stirring [8] or aeration, whereby the average density of the target decreases and the effective electron penetration depth increases [9]. In resent years, nanosecond pulse low-energy electron accelerators capable of operating at a high repetition rate (50 – 400 Hz) have been developed [10, 11], which possess the advantages of long working life, small dimensions, and relatively low cost. Low-energy electron beams of nanosecond pulse duration, characterized by high absorbed radiation dose rates per pulse, can be used for the sterilization of radiation-unstable preparations (some vitamin solutions, enzymes, etc.), since the doses required for sterilization under such conditions are significantly (3 – 10 times) lower [12, 13]. One possible variant of drug powder sterilization by low-energy electron beams is implemented in an experimental setup developed at Pharmaceutical Chemistry Journal Vol. 36, No. 12, 2002