Pharmaceutical Stopper-Flange Sealing for Cryogenic Storage
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Solution Overview
Problem
Existing pharmaceutical container closures made of synthetic rubbers fail to maintain seal integrity at low temperatures due to reduced elasticity, leading to potential contamination and loss of biological materials stored at temperatures below the glass transition temperature of conventional elastomers.
Innovation Solution
A sealed pharmaceutical container design featuring a stopper with a sealing portion that has a radial dimension less than the sealing region of the upper surface, compressed against the container's upper surface by a cap, ensuring the outer peripheral edge of the sealing surface lies radially inward of the transition region, maintaining a uniform contact pressure and seal even at low temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional synthetic rubber stoppers are used for sealing pharmaceutical containers, then the closure system is simple and easy to manufacture, but the elasticity of the stopper reduces at low temperatures (below -30°C), causing seal failure and potential contamination
Solution Approach 1:
The patent changes the material parameter by selecting elastomers with glass transition temperatures below -50°C (such as polybutadiene, polyisoprene, or silicone rubber) to maintain elasticity and sealing performance at cryogenic storage temperatures of -40°C to -196°C, resolving the contradiction between seal reliability and temperature adaptability
Solution Approach 2:
The patent employs composite sealing assemblies combining elastomeric stoppers with overmolded thermoplastic or thermosetting polymer layers that have different thermal expansion coefficients, creating a multi-material system that maintains seal integrity across extreme temperature ranges while accommodating dimensional changes of glass containers
2Reliability
If the stopper sealing portion contacts the transition region of the flange, then the sealing area is maximized, but dimensional changes at low temperatures cause non-uniform contact pressure and seal failure
Solution Approach 1:
The patent applies local quality by designing the sealing portion of the stopper with a radial dimension that is specifically smaller than the sealing region radius of the flange, ensuring contact is confined to the upper surface sealing region with uniform dimensional stability, avoiding the transition region where non-uniform contact pressure occurs at low temperatures
Solution Approach 2:
The patent segments the flange surface into distinct functional zones: a sealing region with uniform dimensions for reliable sealing contact, and a transition region with varying dimensions for structural support, allowing the stopper to contact only the appropriate sealing region and maintain uniform contact pressure across the seal interface
3Reliability
If high compression force is applied to the stopper to maintain seal at low temperatures, then seal integrity is improved, but the risk of vial damage and production costs increase
Solution Approach 1:
The patent changes the material parameter by using elastomers with low glass transition temperatures that maintain high elasticity and sealing force at cryogenic temperatures without requiring excessive compression, thereby protecting glass vials from damage during crimping while ensuring reliable seals at storage temperatures
Solution Approach 2:
The patent applies preliminary action by pre-compressing the stopper during the crimping process to establish optimal contact pressure and seal geometry before storage, ensuring the seal remains intact at low temperatures without requiring excessive force that could damage the glass container
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The design maintains container closure integrity with lower residual seal forces, reducing the risk of vial damage and contamination, and ensures helium leakage rates below 1.4×10−6 cm³/s at temperatures as low as −180°C.
Implementation Method 1
a cap compressing the stopper against the upper surface
Implementation Method 2
The elasticity of typically-used closure materials, however, may reduce at low temperatures
Implementation Method 3
Closures are typically made of synthetic rubbers and other elastomers. Such materials beneficially have high permeation resistance
Data Source
AI summary
A sealed pharmaceutical container comprises a flange comprising an underside surface, an outer surface extending from the underside surface, the outer surface defining an outer radius ro of the flange; and an upper surface extending between the outer surface and an inner surface defining an opening in the sealed pharmaceutical container. The upper surface comprises a sealing region extending between the opening and the outer surface and comprising a radius rsr that is less than ro. The sealed pharmaceutical container also comprises a sealing assembly comprising sealing portion in contact with the upper surface at a lower surface of the sealing portion and a cap compressing the stopper against the upper surface. After compression, the sealing portion of the stopper comprises a compressed radius rsc that is less than rsr adjacent the upper surface.