Closure-drug interactions, types

There are four general types of closure-drug interactions ... 

Interactions with Closure Systems. Elastomeric and plastic container and closure systems release leachable compounds into the liquid dosage form, such as nitrosamines, monomers, plasticizers, accelerators, antioxidants, and vulcanizing agents [44], Each type of container and closure with different composition and/or design proposed for marketing the drug or physician s samples has to be tested and stability data should be developed. Containers should be stored upright, on their side, and inverted in order to determine if container-closure interactions affect product stability [6,45]. 

For drug preparations that will be used for internal or mucous membrane administration (i.e., parenteral preparations, ophthalmics, creams and salves, etc.), additional testing must be performed to assure that any leachants will not cause biological reactions that may be detrimental to the patient. To do this, a test protocol has been established that screens materials used in containers to test for biological interactions. This protocol should be applied to any plastic container closure systems regardless of the type of container that will directly contact pharmacopeial preparations in storage before they are invasively used. This includes all closure systems for parenteral vials. ... 

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