Elastomeric closures

An elastomeric closure is a packaging component that is, or may be, in direct contact with a drug product. Elastomer selection for parenteral packaging principally involves consideration of chemical, physical, and biological properties, with emphasis on the stability profile of the drug/container system. Typical elastomeric closure compositions are listed in Tables 1 1. Although certain packaging applications frequently call to mind certain elastomer types, it is not feasible to prescribe specific... 

In addition to normal compression set test conditions, usually 22 hours at 70 °C in a hot air oven, pharmaceutical elastomeric closures may be subjected to compression set conditions simulating steam sterilization cycles in an autoclave for 30 minutes at 121 °C. Also, sterilizing cycles employing ETO, radiation, or dry heat are used. Comparison data between formulations are used to develop compression set values that will identify potentially acceptable compounds under these conditions. 

An additional consideration under mechanical properties is the characterization of formulation performance by measuring solvent resistance. This parameter is defined as the ability of an elastomeric closure to retain original mechanical and physical properties without undue dimensional change, decomposition or... 

The ideal elastomeric closure is nonreactive physically and chemically, a complete barrier to vapor/gas permeation, easily penetrable via needle or spike, re-sealable, resistant to coring and fragmentation, and maintains package integrity at the seal surface. 

Vacuum retention determines the ability of an elastomeric closure to maintain vacuum in a container-closure system when vacuum retention is a requirement. In certain instances it impacts on the long-term stability of a parenteral system. 

Needle penetration and resealability measures the force required to penetrate the target area of an elastomeric closure with a hypodermic needle and the ability of the closure to reseal when the needle is withdrawn. 

Procedures that facilitate the characterization of extractables from elastomeric closures are important to both manufacturers of closures and injectable drug products... 

By employing both instrumental and conventional analytical techniques on solvent extracts of an elastomeric closure formulation, extractables can be isolated, the inorganic ions determined quantitatively, and the organic components functionally characterized... 

Polyethylene and polystyrene are examples of plastics subject to environmental stress cracking. Crack resistance tests have shown that surfactants, alcohols, organic acids, vegetable and mineral oils, and ethers provide an active environment for stress cracking of polyethylene. Table 6 lists typical sterile devices and plastic materials used to fabricate them, while Tables 7-9 list the potential effects of sterilization processes on polymeric materials. The effect of gamma irradiation on elastomeric closures has been studied by the Parenteral Drug Association [15]. 

Elastomeric closures Evaluation of significant performance and identity characteristics. Parenteral Drug Association Inc. Technical Methods Bulletin No. 2. 

C. J. Milano and L. Bailey. Evaluation of current compendial physiochemical test procedures for pharmaceutical elastomeric closures and development of an improved HPLC procedure. J. Parenter. Sci. Technol., 53, 202 (1999). 

Effects of gamma irradiation on elastomeric closures. Technical Report No. 16. Parenter. Sci. Technol., 50, 1 (1992). 

Elastomeric Closures Closures for pharmaceutical products are generally made of polymeric materials, which may be of either a synthetic or natural origin. While brittle closures such as screw caps are made of conventional thermoplastics with a single composition, elastomeric closures are made of complex mixtures of many... 

The polymeric materials usually used to manufacture rigid closures are practically the same as those seen under plastic containers (Section 6.1.3.2). The same impurities are therefore to be expected in these packaging components. On the other hand, though made of polymeric materials, elastomeric closures present a different structure. In the manufacture of rubber, elastomer, the chief component, is combined with other chemicals to produce a material with specific properties that meet target needs, such as its above-mentioned ability to reseal on repeated use. Table 28 lists the common elastomers used in the pharmaceutical industry and their monomeric structures. 

The substances listed in Table 28 correspond to the basic structure of elastomeric closures. The other components in rubber formulations are curing or vulcanizing agents, accelerators, activators, antidegradants, plasticizers, fillers, and pigments. The most common additives used to compound rubber for the pharmaceutical industry are listed in Table 29. The amount of each component may vary from rubber to rubber, and, depending on the component, the amount can reach more than 50% of the total mass of a formulation. While accelerators are used in amounts of around 1%, fillers may make up more than 50% of the formulation mass. 

The tests, however, are neither qualitative (in the sense of showing which substances can be extracted) nor specifically quantitative since they are conceived to show only the total amount of extractable as a residue. USP (381) Elastomeric Closures for Injection, for example, recommends the calculation of the weight of the residue after evaporating the solvent (purified water, drug vehicle, or isopropyl alcohol) used for extraction. Tests in vivo are recommended only when the material does not meet the requirements of the in vitro tests. 

Even though there is no specific pharmacopeial prescription for testing these materials, they should present the same profile stipulated for container and closures. In the case of tubing lines, which are also made of elastomeric materials, an extractabihty test for elastomeric closures is recommended, mainly for those made of PVC. 

A change from a glass ampule to a glass vial with an elastomeric closure. 

Changes that add or delete silicone treatments to container closure systems (such as elastomeric closures or syringe barrels). 

Smith EJ, Nash RJ (1986) Elastomeric Closures for Parenterals. In Pharmaceutical dosage forms Parenteral Medications, vol 2. Marcel Dekker, New York, p 155... 

Parenterally formulated biopharmaceuticals are typically packaged in glass containers with rubber/synthetic elastomeric closures. Pharmaceutical glass is composed primarily of silicon dioxide tetrahedron which is modified with oxides such as sodium, potassium, calcium, magnesium, aluminum, boron, and iron [45],The USP classifies glass formulations as follows ... 

Bontempo, J. A. (1997), Considerations for elastomeric closures for parenteral biophar-maceutical drugs, in Bontempo, J. A. Ed., Development of Biopharmaceutical Parenteral Dosage Forms, Marcel Dekker, New York. 

Sterile powders or powders for injection may need to be protected from exposure to water vapor. For elastomeric components, data showing that a component meets the requirements of U.S. Pharmacopeia (USP) elastomeric closures for injections will typically be considered sufficient evidence of safety. 

The USP physicochemical tests for extractables should be a part of all suitability programs, regardless of the criticality of the drug dosage form. USP elastomeric closures for injections should also be a part of the extractables study to establish safety. These USP tests, which have evolved over many years, are relevant, sensitive, rapid, and inexpensive. They help establish material safety. 

Elastomeric closures for injections, biological test procedures, physicochemical... 

Critical Steps in the Preparation of Elastomeric Closures for Biopharmaceutical Freeze-Dried Products... 

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