Interaction of rubber closures with powders for parenteral administration

The migration of volatile components into the headspace of vials sealed with rubber closures is a potential source of haze formation in solutions of reconstituted powders for parenteral administration. Different types of vial closures were examined to determine their propensity to release volatile compounds. It was possible to accumulate the volatiles in a cold trap by means of thermal desorption and dynamic headspace. Gas chromatography coupled with mass spectrometry was then used to characterize the volatiles isolated. Components found in the headspace of butyl and halogenated butyl rubber closures included saturated hydrocarbons, unchlorinated or chlorinated olefins, alkylbenzenes, and low molecular weight polydimethylsiloxanes.