Rubber Coring of Injectable Medication Vial Stoppers: An Evaluation of Causal Factors

Abstract

AbstractPurpose:Coring of a medication vial’s rubber stopper has been reported as a major cause of visible particle presence in injectable preparations. In this study, we investigated and quantified visible particle formation caused by coring associated with four potential causal factors.Methods:The factors studied were: nature of the rubber stopper; rubber stopper thickness, type of metal needle bevel used to pierce the stopper, and puncture technique. For each one of 16 different situations, 40 medication vial rubber stoppers were punctured, and the contents filtered. The filters were then examined under optical microscopy and particles present counted and measured.Results:The incidence of particle formation ranged from 0 % to 75 %, depending on the situation. Particle length was on average of 0.98±0.39 mm. The situation that gave the most particles (75 %; 30/40) was obtained when using a short bevelled needle, a 4 mm thick chlorobutyl vial stopper and with a puncture angle of 90°. Whilst a puncture technique reduced particle formation by more than 50 % for the most at risk situation, but without eliminating particle formation (residual formation of 22.5 %; 11/40), the use of a blunt bevelled needle totally eliminated the incidence of visible particle creation. The thickness of the rubber and the nature of the elastomer seemed to be linked to coring incidence, but in lesser proportions.Conclusion:Puncturing the stoppers using a technique with a 45° puncture angle reduced particle formation, but only the use of a blunt metal needle totally eliminated it.