Rubber leachables

Nandanan et al. [35] reported the utilization of linseed oil as an MFA in nitrile rubber vulcanizates. Linseed oil not only acted as a plasticizer but also as the fatty acid component of the activator in the NBR vulcanizates. Use of linseed oil gave appreciable increase in properties like tensile strength, tear resistance, etc. while the viscosity of the compound was marginally lower than that of the control compound (which used di-octyl phthalate as the plasticizer). The vulcanizates containing linseed oil also exhibited increased cure rate as well as reduced leachability compared to the control at a dosage of 2-5 phr. This loading was seen to replace 6 phr DOP and 2 phr stearic acid in conventional NBR vulcanizates thereby reducing compound costs. 

MS is not the only highly sensitive and selective detection system that can be interfaced with GC. For example, consider another compound class of special safety concern as extractables/leachables, A-nitrosamines.f A-Nitrosamines are formed during mixing and vulcanization of certain types of rubber, by the reaction of various secondary amines with nitrosating agents " and can be found at trace levels (ng/g) in components fabricated from these rubbers. 

ISO 9924-2 2000 Rubber and rubber products — Determination of the composition of vulcanizates and uncured compounds by thermogravimetry — Part 2 Acrylonitrile-butadiene and halobutyl rubbers ISO 10356 1996 Cinematography — Storage and handling of nitrate-base motion-picture films ISO 10993-17 2002 Biological evaluation of medical devices — Part 17 Establishment of allowable limils for leachable substances... 

Belsito, D.V. (1990) Contact urticaria caused by rubber. Analysis of seven cases. Dermatol Clin. 8, 61-66 Questions whether increased demand for latex may have decreased quality with more allergens leachable. 

The absorption of other volatiles from the stopper may not lead directly to a solubility issue but are still leachables in the drug. Examples of this are breakdown products of a peroxide-cured rubber formulation. Alcohols and ketones are examples of some of these resultant leachables. 

What is true for the container in the container-closure system is equally true for the closure alone and, essentially, for the elastomeric stoppers, generally butyl rubber, which cap the vial. Fran DeGrazio from West Pharmaceutical Services has done a lot of research in this field and studied many alternatives to their formulation trying to keep down the extractables (essentially volatile) and leachables and prevent adsorption of oils, waxes, polymers, and others on the freeze-dried plug. 

---