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 °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 °C/40 °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.