Sterilisation von Parenteralia mit Mikrowellen als Alternative zur Autoklavierung
Prof. Dr. Georg Heuna und Steliyan Tinkovb
Hochschule Anhalt (FH), Fachbereich 7a, Köthen, und Medical University, Faculty of Pharmacyb, Sofia (Bulgarien)
Sterilization of Parenterals with Micro-waves as an Alternative to Autoclavation
The terminal sterilization of pharma ceutical injections and infusions is prefer ably performed in industry with saturated steam at 121 °C in an autoclav. It has to be assured by validation that the final temperature in all preparations is maintained over 15 min. Concerning the antimicrobial efficiancy this method is regarded as safe. Problems may arise caused by the long time heating of thermolabile drugs. Another potential risk is the interruption of the production continuity by this process.
A very rapid heating of water containing preparations can be achieved by microwave irradiation. Typically, a frequency of 2450 MHz is used. Especially for the sterilization of food but also of pharmaceutical preparations a lot of scientific studies from the last 30 years are at hand. In addition to the thermal microbial inactivation a non-thermal microwave effect is frequently discussed, that might be caused by interactions of the electromagnetic radiation with cell structures or membranes.
Mainly technical problems with the control and regulation of temperature of the preparation in the closed bottles and ampoules and the mechanical stress caused by the resulting internal pressure have by now impeded a commercial use of microwaves for the terminal sterilization of pharmaceutical preparations. The Japanese Pharmacopoeia is the only pharmacopoeia that currently includes microwave irradiation as a terminal sterilization method for aqueous parenterals. As mechanism of microbial inactivation only the heat generated by microwave radiation is recognized.
A microwave sterilizer is currently used in Japan. After successful process development and validation, sealed ampoules containing 1 or 2 ml drug solution are heated by microwave irradiation up to 140-160 °C in a continuous inline process. Subsequently, the final temperature is maintained over 12 s for sterilisation. As an essential advantage compared to the conventional autoclave method, the microwave sterilizer provides for an enhanced stability of thermolabile drugs, a higher safety level of the product by temperature control of all am-poules through infrared pyrometers, and an integration of the sterilistion in an continuous in-line process from the filling to the end-of-line packaging.
Key words Mikrowellensterilisation, nicht-thermische Effekte · Mikrobielle Inaktivierung · In-line-Sterilisation