The protective action of epoxy lining on rubber stoppers of natural, neoprene, and butyl rubber was evaluated against unlined stoppers of the same composition for sorption of reservative from vial solutions and extractives leached from closures into the sofution. For the preservatives tested-namely, P-chloro-8-phenylethyl alcohol and its nonchlorinated analog, phenylethyl alcohol-no protective action against sorption was exhibited by the lined closures. The solutions used in the extractives study were water, 10 per cent ethanol, 50 per cent polyethylene glycol 300, 50 per cent N,N-dimethylacetamide, and 2 per cent benzyl alcohol. The lining on the closures was found to afford protection against leaching. For both the sorption and extractives studies, the butyl rubber closures exhibited optimal stability.
ECENT PUBLICATIONS from this laboratory and R others have shown that rubber closures used for multiple-dose vial solutions can b e detrimental to the stability of the vial contents through sorption of materials from solution (1-7) or through the action of closure extractives on the solution (7-10). To alleviate these inadequacies, one approach used by certain rubber stopper manufacturers is to line the closure surface that will come in contact with the vial solution with a lacquer containing polymeric materials as its major component. Lacquered stoppers have been in use as closures for multiple-dose vial solutions for about 5 years. However, reports relative to the effectiveness of the linings against sorption of materials from solution into the rubber and leaching of extractives from the rubber by the solution appear to be lacking.
Accordingly, this study was initiated to determine the degree of protection against sorption and leaching contributed to the rubber stopper by an epoxy lining. Lined and unlined natural, neoprene, and butyl rubber stoppers were used in the evaluation. The sorption characteristics were tested with aqueous solutions of the preservatives, phenylethyl alcohol and p-chloro-B-phenylethyl alcohol, stored in multiple-dose vials. The leaching tendencies of 10% ethanol, 50% polyethylene glycol 300, 50% N, Ndimethylacetamide, 2% benzyl alcohol, and water on the stoppers were evaluated. Identification of the extractives leached from the stoppers was performed.