Container closure/stoppers

Formulation, Aggregation, and Container Closure/Stopper Considerations... 

Parenteral products should be formulated to possess sufficient buffer capacity to maintain proper product pH. Factors that influence pH include product degradation, container and stopper effects, diffusion of gases through the closure, and the effect of gases in the product or in the headspace. However, the buffer capacity of a formulation must be readily overcome by the biological fluids thus, the concentration and ratios of buffer ingredients must be carefully selected. 

The dye ingress challenge test is performed at the end of expiry to show container-closure integrity over the production shelf life. Dye ingress testing is performed on vials having rubber stoppers exposed to the maximum exposure time and temperature during sterilization cycle. 

A packaging component means any single part of a container closure system. Typical components are containers (e.g., ampules, vials, bottles), container liners (e.g., tube liners), closures (e.g., screw caps, stoppers), closure liners, stopper overseals, container inner seals, administration ports [e.g., on large-volume parenterals (LVPs)], overwraps, administration accessories, and container labels [4],... 

Cork has been used as material for container closures dating back to ancient Egypt but cork stoppers as glass bottle closures have only been used for less than 300 years, replacing wooden stoppers that were hemp-wrapped and soaked in olive oil. The introduction of cork stoppers as wine botde closures is attributed to the French Benedictine Dom Pierre Perignon (1639-1715) who is known for his instrumental role in the evolution of sparkling wine production. In 1750, the first commercial cork stopper factory was established on the Spanish-French border. 

Kirsch, L.E. Nguyen, L. Moeckly, C.S. Pharmaceutical container/closure integrity I Mass spectrometry-based helium leak rate detection for rubber-stoppered glass vials, PDA. J. Pharm. Sci. Technol. 1997, 51, 187-195. 

The container/closure system, which consists of the elastomeric stopper and the glass vial, impacts the elfectiveness of the lyophilization process in two fundamental ways ... 

The volume of production over a period of time is defined as throughput. Throughput can be affected by problems with the container/closure system such as vial breakage, incomplete stoppering, extended drying times for closures, or poor sublimation rate due to a poor package design. 

Residual silicone oil is immiscible with water and disperses in aqueous solutions, appearing as a haze or a suspension of fine particles. Therefore, excess silicone oil present on stoppers could contaminate a pharmaceutical product. In lyophilized products, only the prelyophilization and the reconstituted solutions are subject to contact with the stopper. However, components of the container closure system have been shown to create a residue in the container when water for injection only was lyophilized [3]. Silicone oil was one component of the residue. 

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. 

A container essentially has three characteristic features which may be either separable or inseparable, depending on the container. These three features are the container itself, the label (usually and preferably attached to the container) and the closure. A stoppered jar with an attached adhesive label is an example of a container in which the three features are separable. A polyethylene bag with an opaque label area and a press-together closure is an example of a container in which the features are inseparable. 

The (provide vial size) vial used for the filling of (product name) USP and the media fill run study are the same in dimension and in conformity to glass container requirements as dehned by USP <66l> and EP3.2.1. The stoppers are made up of bromobutyle-based robber formulation, conform to EP 3.2.9 (type I closure), ISO 8871, Current USP, JPXII, and are sterilizable Tyvek bags. The aluminum flip-cap seals used meet the PDA regulation 21 CFR 177.1520 (c) (1.16). 

After preparation, all pure products should be stored in suitable clearly and permanently labelled containers. The bulk samples of stable solids and liquids may be stored in screw-capped and ground glass stoppered bottles respectively. Hygroscopic samples, or those liable to decomposition by contact with atmospheric moisture, should either be stored in a desiccator or in a bottle which is sealed by painting over the closure with molten paraffin wax. Where there is a possibility of photochemical decomposition of chemicals it is general good practice to keep them out of direct sunlight and to store them in brown bottles. 

Labeling and components Unit labels Unit cartons Package inserts Shipping cartons Containers and closures Vials Syringes Stoppers Crimps (seals)... 

The rapid diffusion of A -tetrahydrocannabinol into the plastic of containers and into the rubber stoppers normally used as closures for plasma vials (70 - 96%) and the significant binding to glass at low tetrahydrocannabinol concentrations (20 and 40% at 0.1 and 0.05 Ug/ml, respectively, in 50 ml volumetric flasks) definitely demand careful techniques in the handling, storage, and assay of this compound from aqueous and biological fluids. In fact, the results of any pertinent study where these conditions were not held in account should be quantitatively suspect. 

Rubber stoppers are also efficient, simple, temporary system closures. Properly drilled, stoppers can support thermometers or funnels. Because new stoppers have no surface cavities or cracks, there is no risk of leaks as with corks. Like corks, stoppers are used to keep things in (or out) of container. Table 1.7 includes a list of rubber stopper sizes. 

Stoppers, as opposed to corks, can react with a number of organic chemicals used in the laboratory. Likewise, a concern when using stoppers is that the closure not adversely affect the contained sample. For this reason, cork stoppers are often preferred when containing organic solvents. If you do not have any corks, you may use a rubber stopper that has been enclosed with an aluminum foil cover. This technique has a few limitations The covered rubber stopper will not grip into the seal (there is no friction to hold it in), and the crevices of the foil provide many potential small leaks. 

Ground joint stoppers and snap-on plastic caps are commonplace, but many laboratory containers do not come with built in stoppers or seals. In the absence of a formal closure, or closures such as corks or rubber stoppers, there is the covering film, PARAFILM M . ... 

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