title: Contamination of semi-solid dosage forms by leachables from aluminium tubes.
abstract: The objective of this study was to determine to what extent bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE) and its derivatives are extractable from epoxy-based coatings of aluminium tubes for pharmaceutical use and to monitor their leaching into different kinds of semi-solid dosage forms. Migration increasing factors should be evaluated. Extraction tests using acetonitrile for 10 days at 40 degrees C turned out to be suitable to estimate the maximum amount of extractables. A plain variability in the nature and amount of extractables among tubes of different vendors (n=7) could be demonstrated. Leaching of the remnants into various semi-solid drug products (ointment, cream, gel) during storage (30 degrees C/40 degrees C) was verifiable. Leachable profiles were, apart from storage time and temperature, decisively influenced by the matrix. In particular, matrix polarity seemed to play a crucial role. Thus, the highest amount of leachables was found in isopropanol-based carbomer gel. Furthermore, in-use conditions (mechanical stress) enhanced migration significantly. In order to ensure quality and safety of semi-solid formulae, interactions between the coating material and the drug product should be thoroughly evaluated.
authors.affiliation: Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
authors.forename: Jan Boris
authors.initials: JB
authors.lastname: Haverkamp
authors.forename: Uwe
authors.initials: U
authors.lastname: Lipke
authors.forename: Thomas
authors.initials: T
authors.lastname: Zapf
authors.forename: Rudolf
authors.initials: R
authors.lastname: Galensa
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lipperheide
mesh_terms: D000535:Aluminum / Q000737:chemistry*; D001559:Benzhydryl Compounds; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004340:Drug Contamination; D004349:Drug Packaging; D004356:Drug Storage; D004852:Epoxy Compounds / Q000009:adverse effects / Q000032:analysis*; D005079:Excipients / Q000737:chemistry; D006801:Humans; D010636:Phenols / Q000009:adverse effects / Q000032:analysis*; D015203:Reproducibility of Results; D018570:Risk Assessment; D013696:Temperature; D013997:Time Factors; D000098826:Bisphenol A Compounds
chemical_list: D000535:Aluminum; D001559:Benzhydryl Compounds; D004304:Dosage Forms; D004852:Epoxy Compounds; D005079:Excipients; D010636:Phenols; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds; C006780:bisphenol A