Illustration by Zak Ouart, courtesy of GLS Corp. (McHenry, IL)
Designers and manufacturers of medical devices face challenges that are driving the adoption of next-generation thermoplastic elastomers (TPEs). The materials give designers new flexibility for processes such as part consolidation. Their user-friendly properties often make them preferable to thermoset rubbers, which can be cumbersome and coarse. Also, TPEs can be molded using the same injection molding and blow molding equipment as traditional materials, allowing them to be integrated into the manufacturing process rather than requiring separate operations for creation and assembly, as is the case for thermoset parts. Further, TPEs enable techniques such as overmolding on a variety of substrates.
What Are TPEs?
Thermoplastic elastomers are generally low-modulus, flexible materials. They can be stretched repeatedly to at least twice their original length at room temperature and return to their approximate original length when stress is released.1 Originally, thermoset rubbers such as styrene butadiene rubber (SBR), latex, and polyisoprene were used in applications requiring such elasticity. In many situations, injection-moldable TPEs have replaced these rubbers.
TPEs and the Medical Industry
TPEs have been used for several years in the medical industry. They were initially adopted as replacements for SBR, latex, and polyisoprene. Those materials did not offer design freedom, and TPEs had similar stress-strain performance. TPE materials can also be easily extruded, which makes them appropriate for tubing and elastic bands. Characterized by softness and suppleness, TPEs also appeal to consumers and are therefore popular for many healthcare products used in a home setting.
Early TPE formulations were considered for thermoset stopper replacement in syringes but failed to meet performance requirements. New formulations and other advances, however, have improved performance of TPEs for stopper applications. As TPE technology has evolved, these materials are being considered for overmolded designs to enhance the feel, ergonomics, and aesthetics of the final part.
Desirable attributes such as softness and ease of molding provide opportunities for TPE use in medical applications such as orthopedics, surgical equipment, syringe plungers, needle shields, face masks, resuscitator and breathable bags, and home-use medical devices. With new formulations, these materials help to address regulatory, performance, design, and cost requirements.
Overmolding is an injection molding process in which one material (usually a TPE) is molded onto a second material (typically a rigid plastic). If TPEs are properly selected, the overmolding process forms a strong bond between the TPE and the plastic substrate, and that bond is maintained in the end-use environment. Primers or adhesives may not be required for the overmolding process because bonding occurs inside the mold. An optimum bond between the two materials can be achieved using TPEs.
TPEs can be overmolded without the use of harmful solvents, which are required to bond polyvinyl chloride (PVC) to other plastics. Also, TPEs can be overmolded onto acrylic, polycarbonate, polypropylene, polyethylene, and other plastics that are commonly used in medical device applications. In contrast, silicone can only be overmolded onto high-temperature plastics such as polyamides and copolyesters, materials which are not widely used for medical devices.
Overmolded TPE delivers a soft feel, good aesthetics, a good gripping surface, cushioning against impact and vibration, and insulation against electricity and heat. It can be used for arthritic devices, surgical equipment handles, and infant care products, for example.
Using TPEs in place of conventional materials in medical tools offers manufacturers the opportunity to shorten cycle times and secondary operations. For example, TPEs can replace low-density polyethylene (PE) in the blow-fill-seal process for making bottles designed for eye drops and nasal drops. TPEs enhance these applications by providing transparency (as compared with translucent PE) and flexibility. They can also withstand terminal sterilization, including autoclave at 121˚C (the method favored by FDA), which is not possible using a PE.
TPEs can also help to consolidate a multistep process. Traditionally, rubber tips for needle-shield applications were fabricated from thermosets and polyolefins, which required different manufacturing processes followed by sterilization and assembly. TPEs, in contrast, can be injection molded on the same equipment as the PE and polypropylene used for the needle shield. Therefore, these components can be molded, presterilized, and assembled in a cleanroom environment, which could save time and reduce cost.
Further, molding TPEs instead of fabricating thermosets can improve the safety and consistency of the final product. Injection molding is a one-step process, whereas producing thermosets requires three or more steps (see Figure 1). In any molding process, each step introduces the possibility of compromised quality, which can add up to wide variations in the finished product. Medical device manufacturers want zero contamination in incoming products. And thermosets, no matter how many precautions are in place, present a risk of contamination in the end product because of these multiple steps.
Overmolding of TPEs could also provide value for disposable systems used in bioprocessing. One device manufacturer uses overmolding with TPEs in its sterile assemblies for sampling. The TPE tube is bonded to the cap using overmolding technology. This one-piece construction enables direct, aseptic transfer of fluid and avoids potential contamination and product loss from physical or snap-fit connections.
Figure 1. (click to enlarge) The thermoset process (a) involves as many as five steps compared with the thermoplastic process (b), which uses only one or two.
Designers and manufacturers of medical devices may want to consider replacing thermoset elastomers with TPEs for specific reasons related to the plastics’ processing characteristics. For example, potentially leachable heavy metals are used in the curing process for thermoset elastomers. TPEs do not use these heavy metals.
TPEs can also be used as alternatives to latex, polyisoprene, and butyl rubber used in various medical products, such as stoppers, gaskets, and injection ports. TPEs do not emit nitrosamine, mercapto benzo thiazole (MBT), and other byproducts of thermoset elastomers, which are known carcinogens and irritants.2 In addition, the thermoplastics have a broad hardness and flexibility range, as well as clarity, which is not possible using thermoset elastomers. As thermoplastics, TPEs can use a wider range of raw materials to tailor performance properties such as low oxygen and moisture vapor transmission rates (OTR and MVTR) for medical packaging that requires a long shelf life.
Another benefit of TPEs is the level of design innovation that can be achieved. Medical device makers can leverage overmolding capabilities and the precision of injection molding to attain greater design freedom. The thermoset process is limited to compression molding. Injection molding—because of its high pressure and processing speed—makes it possible to mold complex geometries that are not achievable using low-pressure compression molding.
A key focus area for FDA is reducing leachables and extractables from rubber and plastic packaging components. These safety concerns are set forth in FDA’s guidance Container Closure Systems for Packaging Human Drugs and Biologics.3 Leachables can negatively influence patient health when introduced into drugs or other formulations. FDA is concerned about polynuclear aromatics (PNAs), nitrosamine and 2-MBT, among other leachables and extractables. For example, health concerns regarding 2-MBT, a vulcanization accelerator for rubber, have led to reformulation of ethylene-propylene-diene monomer, polyisoprene, and butyl rubber stoppers for parenteral drugs. Similarly, FDA has reduced the acceptable level of volatile n-nitrosamines in rubber baby bottle nipples to 10 ppb. In response to the guidance, many manufacturers are seeking replacement materials.
Because TPEs do not undergo curing, they avoid use of nitrosamines and other hazardous leachables. As such, the materials may provide alternatives to thermosets so that manufacturers can meet regulatory requirements. Further, some TPEs provide very low oxygen permeation, which defends against water loss or absorption.4 For drug-contact applications, these TPEs are inert and demonstrate an extremely low level of extractables and leachables.5
Processing parts using TPEs can limit the number of components, which can also help with the regulatory process. When a significant number of parts are consolidated, regulatory bodies may require less failure testing, because the risk of leaks that could cause cross-contamination has been reduced.
From a design standpoint, TPEs can enable part consolidation to eliminate potential points of failure. Instead of having multiple components mechanically joined together with fittings that could leak or break, TPE overmolding can create a single seamless assembly.
The design flexibility of TPEs also helps manufacturers achieve device miniaturization and improved usability. They can be molded using a high-pressure injection molding process, which helps in thin-wall molding and complex geometries. The combination of hard and soft TPEs (dual-durometer products) enables additional functionality. Although thermoset rubbers may need reinforcing fillers that limit physical attributes such as clarity and density, TPEs do not require such fillers. They can be reinforced using plastics, which allows them to maintain a low specific gravity, as well as clarity and translucence.
In most medical devices, raw materials make up only a portion of the final product cost. There are also costs associated with assembly, quality assurance, validation, and the overall manufacturing process. Although the raw-material price of TPEs on average could be 50% higher than thermosets, TPEs help reduce overall costs by reducing or eliminating scrap, enabling part consolidation, and improving quality. In comparison with thermosets, TPEs can reduce finished part cost by up to 30% through processing efficiency, elimination of secondary processes and their associated materials, and fewer rejects from contamination.6 Further, the ability to process TPEs using conventional molding equipment makes these materials an attractive choice.
Figure 2. (click to enlarge) The oxygen permeability properties at 22°C of thermoplastic elastomers meet or exceed those of other materials.
Manufacturers are also looking for improved barrier materials to extend shelf life and to reduce the extractables from thermosets. TPEs meet the low compression set of thermoset rubbers in usage temperatures. The barrier properties of TPEs not only meet or exceed those of butyl rubber for barrier applications, but also offer other advantages, including lot-to-lot consistency and a wider hardness range (see Figures 2 and 3). They can also be sterilized using autoclave, gamma, and E-beam methods.
Currently, device manufacturers are using traditional materials such as butyl rubber and multilayer films to reduce gas and vapor permeation and provide a high-barrier package. Barrier materials extend product shelf life, protect active ingredients from oxidation and moisture loss or gain, and retain pressure or a vacuum, among other benefits. Some uses include prefilled syringes, parenteral drugs, IV solution and blood collection devices, and delivery systems for insulin and nutritional fluids.
Figure 3. (click to enlarge) A hardness comparison of commonly used plastics.
TPEs can also offer such barrier properties, and they can even surpass butyl rubber in performance and design flexibility. These properties are achieved by compounding TPEs with higher-barrier resins and nanocomposites, which is not possible with thermoset rubbers because they use a different manufacturing process. Nanocomposites and high-barrier resins need to be dispersed well, which requires a high-shear, high-temperature extrusion process. In contrast, thermoset rubber is compression molded with very little shear and at a low temperature, resulting in poor dispersion of these engineering plastics and nanoparticles.
A key area in which TPEs can improve upon traditional barrier materials is the elimination of halogens and heavy metals. Some potential applications include vial stoppers, IV injection ports, and blood collection stoppers. Tin and other heavy metals used in curing thermoset rubbers are undesirable constituents in device packaging. They can potentially leach into the contents or contaminate clean systems, which are increasingly used for disposable devices.
The barrier performance of TPEs can eliminate the need for overwraps that can increase costs and add to the waste stream. For example, one company recently developed an IV solution bag that uses TPE to eliminate the plastic overwrap that usually protects the solution during shipping. Another firm has developed a sterile packaging solution for parenteral drugs using TPE as a laser-weldable stopper to replace a conventional thermoset rubber stopper. The product is an aseptic container (with a preapplied vial stopper) that manufacturers can use for drugs that are sensitive to terminal sterilization such as autoclave, gamma, etc. The vial is filled using a needle that punctures the stopper; subsequently, the needle hole is sealed using a laser to locally melt the stopper. Unlike thermosets, TPEs can be reheated and melted to close the needle insertion point. TPEs have also been used in drug-eluting stents because the high-barrier properties enable controlled release for a long life.7
Replacing PVC and Silicone Rubber
Another key application area for TPEs is replacing PVC and silicone rubber in tubing, bags, and films. The industry is moving away from PVC because of health and environmental concerns. It is virtually the only material that requires phthalate plasticizers (developmental toxins linked to bronchial irritation and asthma) and can include heavy-metal stabilizers (neurotoxins and carcinogens). In addition, during manufacture PVC produces a large number of highly toxic chemicals, including dioxins (potent human carcinogens), vinyl chloride (carcinogen), ethylene dichloride (probable carcinogen), and polychlorinated biphenyls (carcinogens and reproductive and developmental toxins). When incinerated at end of life, PVC releases more dioxins. And even before it ignites, PVC releases hydrogen chloride gas that forms hydrochloric acid upon contact with moisture, including moisture in the lungs of those who inhale it.
Figure 4. (click to enlarge) Various materials are compared in terms of hardness to a clear TPE, which is temperature resistant.
Silicone rubber is very expensive (on average, twice as expensive as TPEs) and is reported to absorb proteins and antioxidants, which could reduce the efficacy of drugs.8,9 Specifically, silicone can absorb protein from biopharmaceuticals, potentially affecting these organisms and upsetting the delicate balance of the media they are carried in.
Soft, clear, temperature-resistant TPEs can replace PVC and silicone rubber while adding performance and design advantages, such as hardness (see Figure 4). TPEs can match or exceed such physical properties of silicone and PVC as clarity and flexibility or low modulus while offering inertness and the ability to withstand various sterilization techniques.
Certain soft and clear TPEs exhibit very low protein absorption, as well as low adsorption and permeability, making them a better choice for tubing used for fluid transfers.9
TPEs offer the formulation freedom to match or exceed the properties of many thermoset offerings for healthcare devices and equipment. Advances in TPE compounding science have helped these versatile materials make significant inroads into a variety of healthcare sectors. The desirable combination of design freedom, system cost benefits, and improved performance characteristics is fueling strong growth of TPEs in a wide range of medical applications.
Raj Varma is commercial innovation manager at GLS Corp. (McHenry , IL). He can be reached at firstname.lastname@example.org.
1. Geoffrey Holden, ed., Thermoplastic Elastomers, 3rd ed. (Cincinnati: Hanser Gardner Publications, 2004), Chap. 1.
2. Alan C Schroeder, “Leachables and Extractables in OINDP: An FDA Perspective,” (paper presented at the ONDQA, CDER, FDA, PQRI L/E Workshop, December 5–6, 2005).
3. “Container Closure Systems for Packaging Human Drugs and Biologics” (Rockville, MD: FDA, May 1999).
4. Masahiro Asada, “Development of New Generation of SBC by Living Carbocationic Polymerization: Synthesis, Performance Characteristics and Potential Applications of SIBSTAR” (paper presented at the TPE Conference, Akron, OH, May 11–12, 2006).
5. J Angus and P Brunelle. 2004. Thermoplastic vulcanizers. U.S. Patent 147,677 A1, filed Dec. 5, 2003, and issued Jul. 24 2004.
6. David Marshall and Hideki Ishikawa, “A Novel Isobutylene-Based TPV” (paper presented at ANTEC, Charlotte, NC, May 2006).
7. James J Barry, “Key Considerations for the Use of Polymer Carriers for Drug Eluting Stents” (paper presented at TPE Conference, Akron, OH, May 11–12, 2006).
8. Judith E Puskas et al., “Polyisobutylene-Based Biomaterials,” Journal of Polymer Science: Part A: Polymer Chemistry 42 (2004): 3091–3109.
9. SaniPure 60 Technical Data Sheet, (Akron, OH: Saint-Gobain Performance Plastics) (available on request at www.medical.saint-gobain.com).