Contamination of semi-solid dosage forms by leachables from aluminium tubes

Eur J Pharm Biopharm. 2008 Nov;70(3):921-8. doi: 10.1016/j.ejpb.2008.06.012. Epub 2008 Jun 24.

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.

MeSH terms

  • Aluminum / chemistry*
  • Benzhydryl Compounds
  • Chemistry, Pharmaceutical
  • Dosage Forms*
  • Drug Contamination*
  • Drug Packaging*
  • Drug Storage
  • Epoxy Compounds / adverse effects
  • Epoxy Compounds / analysis*
  • Excipients / chemistry
  • Humans
  • Phenols / adverse effects
  • Phenols / analysis*
  • Reproducibility of Results
  • Risk Assessment
  • Temperature
  • Time Factors

Substances

  • Benzhydryl Compounds
  • Dosage Forms
  • Epoxy Compounds
  • Excipients
  • Phenols
  • Aluminum
  • 2,2-bis(4-glycidyloxyphenyl)propane
  • bisphenol A