The stopper is the working part of a multi-use vial. It has to seal the vial for years, admit a transfer device repeatedly without leaking or shedding, and contribute nothing to the water. Those three requirements decide the material, the design and the tests.

Material: halobutyl rubber

Stoppers for aqueous sterile products are almost always bromobutyl or chlorobutyl rubber, the halogenated forms of butyl rubber. Butyl rubber has very low permeability to gases and water vapor, so the vial neither loses water nor admits oxygen through the stopper. Halogenation lets the rubber be cured with low levels of additives, which keeps extractables low. The formulation also includes inert fillers and pigments, and the finished stopper is washed and sterilized before use. Natural rubber, which is more permeable and carries more extractables, is not used for products of this kind. See vials: glass vs. plastic, stoppers, crimp seals and flip-off caps.

Coatings and laminates

• Fluoropolymer laminates. A thin film of ETFE or PTFE bonded to the product-contact face of the stopper acts as a barrier between the rubber and the contents, reducing extractables and adsorption. It is common on stoppers for sensitive products and appears on some water vials.
• Silicone. Most stoppers carry a trace of silicone oil or a cross-linked silicone coating applied for machinability, so they do not stick to each other or to filling equipment. It is the source of the occasional silicone droplet seen in particulate analysis.

How stoppers are tested: USP <381>

Elastomeric closures are tested for physicochemical properties (what they release into water, measured as turbidity, color, acidity, UV-absorbing substances, reducing substances and heavy metals) and for functionality: penetrability (the force needed to pass a transfer device through the closure), fragmentation (the number of visible rubber particles produced by a series of entries) and self-sealing capacity (whether a closure entered repeatedly still holds a vacuum and excludes dye). A stopper that passes is fit for a multi-use vial. See how many times can a vial be punctured?

Coring

Coring is the cutting of a small cylinder or fragment from the stopper as a transfer device passes through it. The fragment falls into the contents as a visible particle. It becomes more likely with a blunt or previously used transfer device, with a large-diameter device, with entering the stopper at a shallow angle, with repeated entries at the same point, and with harder rubber. The counter-measures are the mirror image: a fresh sharp sterile device each time, entry perpendicular to the stopper at its thinner central target, and spreading entries across the target rather than stacking them. Any vial in which a fragment is seen is discarded. See particulate matter testing and how to open a vial.

Stopper hygiene

The exposed face of the stopper is not sterile once the flip-off button is removed; it is wiped with 70% isopropyl alcohol and allowed to dry before every entry. See 70% vs. 99% isopropyl alcohol.

Related

Container closure integrity · Type I borosilicate glass · Flip-off caps and crimp seals

All BAC Water Supply products are supplied for laboratory research use only and are not for human or veterinary use.