EVALUATION OF CLOSURE INTEGRITY AFTER MULTIPLE PENETRATIONS

The purpose of this investigation was to simulate in-use testing of cl osures to determine how many doses could be reasonably withdrawn from a multiple dose vial of a product without compromising the integrity o f the closure. Four types of studies were done: 1) a simulated in-use test, 2) a coring test development study, 3) effect of sterilization o n coring, and 4) exploratory studies of closure leakage after multiple penetrations. A modified drill press was used for the studies. West 1 888 and West 1535 closures were evaluated by the simulated in use test using a 26G Needle. The results indicated that few particles were gen erated after 20 penetrations of both closures. There was a marked incr ease in particles after 30 penetrations. When sterilized closures were tested, it was found that West 1888 generated no particles after 10 i nsertions with 21G and 18G needles, but there was an increase in the n umber of particles after 20 insertions. With West 1535, particles were generated after only 10 insertions. Interestingly, autoclaved closure s released fewer particles than closures that were not autoclaved. Lea kage was observed only from West 850 closures and only under relativel y high pressure differential conditions.