The Effects of Autoclaving on the Physical Properties and Biological Activity of Parenteral Heparin Preparations

Abstract

Abstract Heparin ampoules have been autoclaved at 115°C, 121°C, 126°C and 130°C for time intervals up to 50 min and the biological potency and physicochemical integrity of the preparations assessed. The anticoagulant activity, determined with the APTT assay, did not change significantly for the autoclaved samples but a decrease was observed using the BP assay. Autoclaving was also associated with a depolymerization process, as confirmed by high performance liquid chromatography, and the formation of ‘species’ with an absorption in the UV spectrum. However, autoclaving had no detrimental effect on the integrity of the anionic sites on heparin. It is proposed that Maillard-type reactions are responsible for these observations and the results indicate that autoclaving could be used to sterilize parenteral heparin solutions.