Thermal sterilization of heat-sensitive products using high-temperature short-time sterilization.
High-temperature short-time (HTST) sterilization with a continuous-flow sterilizer, developed for this study, was evaluated. The evaluation was performed with respect to (a) the chemical degradation of two heat-sensitive drugs in HTST range (140-160 degrees C) and (b) the microbiological effect of HTST sterilization. Degradation kinetics of two heat-sensitive drugs showed that a high peak temperature sterilization process resulted in less chemical degradation for the same microbiological effect than a low peak temperature process. Both drugs investigated could be sterilized with acceptable degradation at HTST conditions. For the evaluation of the microbiological effect, Bacillus stearothermophilus ATCC 7953 spores were used as indicator bacteria. Indicator spore kinetics (D(T), z value, k, and E(a)), were determined in the HTST range. A comparison between the Bigelow model (z value concept) and the Arrhenius model, used to describe the temperature coefficient of the microbial inactivation, demonstrated that the Bigelow model is more accurate in prediction of D(T) values in the HTST range. The temperature coefficient decreased with increasing temperature. The influence of Ca(2+) ions and pH value on the heat resistance of the indicator spores, which is known under typical sterilization conditions, did not change under HTST conditions.
Mann
A
A
Department of Pharmacy, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Kiefer
M
M
Leuenberger
H
H
D001411:Geobacillus stearothermophilus / Q000254:growth & development / Q000302:isolation & purification; D006358:Hot Temperature; D007700:Kinetics; D015282:Octreotide / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry; D013171:Spores, Bacterial / Q000302:isolation & purification; D013242:Sterilization / Q000379:methods*
D010879:Piperazines; C065286:SDZ EAA 494; D015282:Octreotide