Vial (revision 7)
Old revision·16:07, 8 Aug 2024·Ref_Desk_Ron
| Vial | |
|---|---|
| Function | Primary container for injectable and lyophilised products |
| Usual material | Type I borosilicate glass |
| Closure | Elastomeric stopper with crimped aluminium ferrule |
| Common neck finishes | 13 mm and 20 mm |
| Common sizes for research peptides | 2R and 6R |
| Topic infobox · conventions | |
A vial is a small container, conventionally of glass, closed by an elastomeric stopper retained under a crimped metal ferrule. It is the standard primary package for injectable products and for lyophilised solids, including the great majority of peptides distributed for research use. The vial, its closure and its seal are treated in pharmaceutical practice as a single functional unit — the container closure system — because none of the three performs its function without the others.[1]
The container has three simultaneous duties. It must contain the product without contributing to it, which constrains the chemistry of both glass and elastomer; it must exclude micro-organisms and, for many products, moisture and oxygen, which is a matter of seal integrity rather than of material; and it must permit withdrawal by needle without loss of that integrity, which is why the closure is a penetrable elastomer rather than a screw cap.[2][1]
Failures of each duty are documented and distinct. Leaching of glass constituents alters solution pH and can catalyse degradation; inner-surface delamination sheds glass flakes and was the subject of regulatory advisories and recalls in 2010 and 2011; incomplete sealing permits microbial ingress and moisture gain, the latter raising the residual moisture of a lyophilised cake over its shelf life; and coring of the stopper by a needle introduces elastomer particles into the withdrawn liquid.[3][4][5]
Construction and materials
[edit]Pharmaceutical glass vials are produced by two routes with different characteristics.
Tubing-drawn vials are formed by softening a length of drawn borosilicate tubing and shaping the base and neck. Wall thickness is set by the tubing and is thin and uniform; dimensional tolerances are close; and the process is fast, which makes tubing the route for small vials produced in quantity. Because the neck and base are formed by localised heating, the inner surface at those points reaches higher temperatures than elsewhere and is chemically altered, which is the origin of the delamination susceptibility discussed below.[4]
Moulded vials are formed by pressing molten glass in a mould. Walls are thicker and less uniform, tolerances looser, and the vials heavier and more robust. Moulding dominates for larger containers and where mechanical strength matters more than dimensional precision.[6]
Polymer vials of cyclic olefin polymer or copolymer are established for products incompatible with glass or requiring extreme resistance to breakage. They eliminate delamination and alkali leaching, and they permit lower moisture-vapour barrier performance and different extractable profiles — trade-offs rather than improvements. Requirements for plastic packaging systems are set out in USP <661> and its subsidiary chapters.[7]
| !Type | Composition | Determined by | Typical use |
|---|---|---|---|
| I | Borosilicate | Powdered glass test | Parenterals, including all lyophilised products |
| II | Soda-lime, inner surface treated | Water attack at 121 °C | Aqueous parenterals of suitable pH |
| III | Soda-lime | Powdered glass test | Non-parenteral, and dry powders where permitted |
| NP | Soda-lime, general purpose | Powdered glass test | Non-parenteral only |
Depyrogenation
[edit]Glass vials are rendered free of endotoxin by dry heat, conventionally at 250 °C or above for a validated period, with the requirement expressed as a demonstrated reduction of at least three logarithms in a challenge of bacterial endotoxin rather than as a time and temperature alone. The process is destructive to endotoxin rather than merely sterilising, which is why it is specified separately from sterilisation and why autoclaving does not substitute for it. Verification of the result is by the bacterial endotoxin test described in USP <85>.[8][1]
References
- ^ a b c United States Pharmacopeia, General Chapter <1207>, "Package Integrity Evaluation — Sterile Products" (informational), with subchapters <1207.1> to <1207.3>. USP–NF, current revision.
- ^ United States Pharmacopeia, General Chapter <381>, "Elastomeric Closures for Injections". USP–NF, current revision.
- ^ US Food and Drug Administration. "Advisory to Drug Manufacturers: Formation of Glass Lamellae in Certain Injectable Drugs" (March 2011).
- ^ a b Ennis RD, Pritchard R, Nakamura C, et al. "Glass vials for small volume parenterals: influence of drug and manufacturing processes on glass delamination." Pharmaceutical Development and Technology 6(3):393–405 (2001).
- ^ ISO 8362-5:2016, Injection containers and accessories — Part 5: Freeze drying closures for injection vials, read with ISO 8362-6:2010, Part 6: Caps made of aluminium-plastics combinations for injection vials. International Organization for Standardization.
- ^ ISO 8362-1:2018, Injection containers and accessories — Part 1: Injection vials made of glass tubing, read with ISO 8362-4:2011, Part 4: Injection vials made of moulded glass. International Organization for Standardization.
- ^ United States Pharmacopeia, General Chapter <661>, "Plastic Packaging Systems and Their Materials of Construction". USP–NF, current revision.
- ^ United States Pharmacopeia, General Chapter <660>, "Containers — Glass". USP–NF, current revision.