title: Endotoxin testing in inhalation grade lactose-a useful quality parameter?
abstract: Alpha-lactose monohydrate is the standard carrier used for dry powder inhalation drug products. The physico-chemical characteristics of this carrier material need to be monitored and specified carefully in order to guarantee functionality of the powder formulation. But also microbiological acceptance criteria need to be considered during development and routine testing. In this study, the endotoxin content of 19 batches of alpha-lactose monohydrate provided by two different manufacturers was determined with a semi-quantitative LAL assay. The endotoxin content was found to be less than 18 endotoxin units (EU)/g lactose in all cases and less than 3 EU/g in most cases. Assuming that the typical lactose has an endotoxin content of 10 EU/g and that a patient inhales six times daily 25 mg of lactose and that the total amount of lactose reaches the lung, this translates to an endotoxin exposure of 1.5 EU per day. On the other hand, the proposal for endotoxins in air limits the endotoxin concentration to 50 EU/m3 which corresponds to approximately 3333 EU inhaled endotoxins a day during normal breathing (breathing at rest conditions). The maximum endotoxin exposure by dry powder inhalations is thus two log steps lower than the recommended acceptable daily intake.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany. steckel@pharmazie.uni-kiel.de
authors.forename: Hartwig
authors.initials: H
authors.lastname: Steckel
authors.forename: Franz H
authors.initials: FH
authors.lastname: Furkert
mesh_terms: D000280:Administration, Inhalation; D004337:Drug Carriers / Q000737:chemistry* / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control; D004731:Endotoxins / Q000032:analysis*; D007785:Lactose / Q000737:chemistry* / Q000592:standards; D008033:Limulus Test / Q000379:methods; D011208:Powders; D011786:Quality Control; D013678:Technology, Pharmaceutical
chemical_list: D004337:Drug Carriers; D004731:Endotoxins; D011208:Powders; D007785:Lactose