Effect of Solution Factors on Endotoxin Coagulation State

Abstract

Endotoxin contamination of drugs intended for parenteral use presents a serious problem. Endotoxin removal efficiency differs under various conditions (temperature, pH and solvent). This variation can be related to the endotoxin agglomerate state. There is no direct way to probe endotoxin agglomerate state. In this study, the endotoxin agglomerate size was measured directly by a nanoparticle-size instrument and endotoxin removal efficiency was indirectly analyzed under the same conditions with ultrafiltration technology. Direct–indirect analysis of endotoxin agglomerate state was established. We investigated the mechanisms of this interference and found that temperature, pH and ethanol exerted significant effects on endotoxin removal from water solutions and endotoxin coagulation size. Endotoxin removal efficiency and endotoxin agglomerate size were determined under varying temperatures, pH levels, and ethanol concentrations by ultrafiltration and by using an endotoxin nanometer particle size analyzer. When the temperature was increased from 10 to 60 °C, the endotoxin agglomerate size and endotoxin removal efficiency increased. When pH was increased from 3 to 10 and ethanol concentration raised from 10 to 30 %, the endotoxin agglomerate size and the endotoxin removal efficiency decreased. This study provides reference data for endotoxin removal and improves injection safety.