Depyrogenation of pharmaceutical solutions using submicron and ultrafilters.

Abstract

The effect of varying the pH and ionic strength on endotoxin removal (depyrogenation) from Water for Injections (WFI) was investigated. Studies using submicron filters showed that endotoxin aggregation and filter retention increased with increasing molarity and decreasing pH. Using a Sartorius 0.01 micron filter, greater than 98% endotoxin retention could be achieved with 10 endotoxin units (EU)/ml bulk solution, and greater than 97% endotoxin retention with the 500 EU/ml bulk solution. Depyrogenation of active and placebo solutions of the radiopaque, Iohexol (350 mgI/ml), using ultrafilters of varying nominal molecular weight limit (NMWL 10,000-300,000) and a Pall Posidyne 0.2 micron filter was also investigated. Results with the ultrafilters showed that it was possible to increase the molecular weight cut-off of an ultrafilter from 10,000 to 100,000, without affecting the efficiency of endotoxin removal, thereby increasing flow rate and reducing filtration time. The Posidyne filter was able to depyrogenate Iohexol active and placebo product. The use of submicron filtration in place of ultrafiltration would provide significant cost benefits in terms of filtration time and equipment costs, and they have been shown to be capable of efficient depyrogenation of these pharmaceutical products.