Evaluation of closure integrity after multiple penetrations.

Abstract

The purpose of this investigation was to simulate in-use testing of closures to determine how many doses could be reasonably withdrawn from a multiple dose vial of a product without compromising the integrity of the closure. Four types of studies were done: 1) a simulated in-use test, 2) a coring test development study, 3) effect of sterilization on coring, and 4) exploratory studies of closure leakage after multiple penetrations. A modified drill press was used for the studies. West 1888 and West 1535 closures were evaluated by the simulated in-use test using a 26G Needle. The results indicated that few particles were generated after 20 penetrations of both closures. There was a marked increase in particles after 30 penetrations. When sterilized closures were tested, it was found that West 1888 generated no particles after 10 insertions with 21G and 18G needles, but there was an increase in the number of particles after 20 insertions. With West 1535, particles were generated after only 10 insertions. Interestingly, autoclaved closures released fewer particles than closures that were not autoclaved. Leakage was observed only from West 850 closures and only under relatively high pressure differential conditions.