Contamination of semi-solid dosage forms by leachables from aluminium tubes.
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.
Haverkamp
Jan Boris
JB
Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
Lipke
Uwe
U
Zapf
Thomas
T
Galensa
Rudolf
R
Lipperheide
Cornelia
C
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
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