title: Matrix effect on leaching of Bisphenol A diglycidyl ether (BADGE) from epoxy resin based inner lacquer of aluminium tubes into semi-solid dosage forms.
abstract: To study the impact of different semi-solid dosage form components on the leaching of Bisphenol A (BPA) and Bisphenol A diglycidyl ether (BADGE) from the epoxy resin-based inner lacquer of aluminium tubes, the tubes were filled with different matrix preparations and stored at an elevated temperature. Despite compliance with the European Standards EN 15348 and EN 15766 on porosity and polymerisation of internal coatings of aluminium tubes, the commercially available tubes used in the study contained an increased amount of polymerisation residues, such as unbound BPA, BADGE and BADGE derivatives in the lacquer, as determined by acetonitrile extraction. Storage of Macrogol ointments in these tubes resulted in an almost quantitative migration of the unbound polymerisation residues from the coating into the ointment. In addition, due to alterations observed in the RP-HPLC chromatograms of the matrix spiked with BADGE and BADGE derivatives it is supposed that the leachates can react with formulation components. The contamination of the medicinal product by BPA, BADGE and BADGE derivatives can be precluded by using aluminium tubes with an internal lacquer with a low degree of unbound polymerisation residues.
authors.affiliation: Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. Electronic address: Uwe.Lipke@bfarm.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lipke
authors.affiliation: LTS Lohmann Therapie-Systeme AG, Andernach, Germany. Electronic address: Jan.Haverkamp@ltslohmann.de.
authors.forename: Jan Boris
authors.initials: JB
authors.lastname: Haverkamp
authors.affiliation: Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. Electronic address: Thomas.Zapf@bfarm.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zapf
authors.affiliation: Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. Electronic address: Cornelia.Lipperheide@bfarm.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lipperheide
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000535:Aluminum / Q000737:chemistry*; D001559:Benzhydryl Compounds / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004304:Dosage Forms; D004340:Drug Contamination / Q000517:prevention & control; D004852:Epoxy Compounds / Q000737:chemistry*; D004853:Epoxy Resins / Q000737:chemistry*; D007764:Lacquer; D009824:Ointments / Q000737:chemistry*; D000098826:Bisphenol A Compounds
chemical_list: D000097:Acetonitriles; D000535:Aluminum; D001559:Benzhydryl Compounds; D004304:Dosage Forms; D004852:Epoxy Compounds; D004853:Epoxy Resins; D009824:Ointments; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds; C032159:acetonitrile
keywords: Aluminium tubes; Bisphenol A (BPA); Bisphenol A diglycidyl ether (BADGE); Epoxy resin-based inner lacquer; Leachates