European Pharmacopoeia (EP) Chapter 3.2.9 Rubber Closures for Containers

European Pharmacopoeia (EP) Chapter 3.2.9 describes the requirements for rubber closures of containers used for aqueous parenteral preparations, powders and freeze-dried powders.

Rubber caps for containers for aqueous parenteral preparations for powders and freeze-dried powders are manufactured from materials obtained by vulcanization (cross-linking) of macromolecular organic substances (elastomers) with suitable additives. This specification also applies to lids of containers for powder and freeze-dried products to be dissolved in water immediately before use.

This specification does not apply to closures, laminated closures or lacquered closures manufactured from silicone elastomer (European Pharmacopoeia (EP) Chapter 3.1.9 Silicone elastomer for closures and tubing). Elastomers are produced from natural or synthetic materials by polymerization, polyaddition or polycondensation. The nature of the main ingredients and various additives, for example vulcanizers, accelerators, stabilizers and pigments, depends on the properties required for the finished product.

Rubber caps are classified into two types:

Type I caps are the caps that meet the most stringent requirements and should be preferred
Type II closures are closures that have mechanical properties suitable for special uses, e.g. multiple drilling, and which, due to their chemical composition, cannot meet as stringent requirements as those in the first category

The caps selected for use with a particular preparation are as follows:

Constituents of the preparation in contact with the closure are not adsorbed onto the surface of the closure and do not migrate into or through the closure to a degree sufficient to adversely affect the preparation
The cap does not yield quantities sufficient to affect the stability of the preparation substances or pose a risk of toxicity

The caps are compatible with the preparation in which they are used throughout the period of validity.

The company manufacturing the preparation must obtain an assurance from the supplier that the composition of the cap has not changed and is the same as that of the cap used during the compatibility test. When the supplier informs the manufacturing company about the preparation of changes in the composition, the compatibility test must be repeated in whole or in part, depending on the nature of the changes.

Rubber caps are elastic, translucent or opaque and do not have a characteristic color. This depends on the additives used. They are practically insoluble in tetrahydrofuran, although significant reversible swelling can occur here. They are homogeneous and practically free of glare and foreign matter, for example fibers, foreign particles and waste rubber.

Identifying the type of rubber used in covers is beyond the scope of this specification. The identification test provided below distinguishes between elastomer and non-elastomer caps but does not distinguish between various types of rubber. Other identification tests may be performed to detect differences in a batch compared to the caps used for compatibility testing. For this purpose, one or more of the following analytical methods can be applied:

Determination of relative density
Determination of sulfated ash
Determination of sulfur content
Thin layer chromatography performed on an extract
Ultraviolet absorption spectrophotometry of an extract
Infrared absorption spectrophotometry of a pyrolysate

Test methods performed within this specification include:

Solution S
Appearance of the solution
Acidity or alkalinity
absorption
Reducing substances
Ammonium
extractable zinc
Extractable heavy metals
evaporation residue
volatile sulphides
penetrability
Fragmentation
self sealing

Briefly, the quality requirements within this specification are:

Components of the pharmaceutical preparation in contact with the cap are not adsorbed and do not migrate into or through the cap
The closure does not release substances in quantities that would affect the stability of the pharmaceutical preparation or pose a risk of toxicity
The cap is compatible with the pharmaceutical preparation (during shelf life)
The closure can be washed and sterilized before use

Among the numerous testing, measurement, analysis and evaluation studies it provides for businesses in various sectors, our organization also provides testing services within the scope of "European Pharmacopoeia (EP) Chapter 3.2.9 Rubber caps for containers" with its trained and expert staff and advanced technological equipment.