Features

The use of multicomponent technology under cleanroom conditions provides an excellent foundation for the development of new medical and pharmaceutical products.

Along with cost savings, coextrusion technology offers improved functionality in new tubing products. This article explores how this micro-dimensional tubing is currently being used to meet increasingly complex medical engineering requirements.

Connector tubes for infusion and dialysis bags.

In many cases, coextrusion of multiple polymer layers in the production of micro-dimensional tubing for medical engineering is still uncharted territory. Microextruders allow for the production of multilayer tubing from up to four different polymer materials. The smallest achievable inner tubing diameter is about 100 μm, with a minimal wall thickness of approximately 50 μm.

Microextruders can work at minimal material throughput rates, with an output of less than 30 grams per hour. These micro-extruders can produce and distribute application-specific layer thicknesses. They can also embed several color stripes or x-ray contrast stripes, integrate functional layers, such as layers that provide light-protection properties or to act as a gas barrier. Micro-extruders also enable the use of bonding agents for incompatible polymers to prevent delamination.

Which Materials Can Be Used?

In theory, any polymer can be used in coextrusion. In practice, however, the thermoplastics that are generally used have already proven their worth in other processing techniques in medical engineering and pharmaceuticals: polyurethanes, polyamides, polyolefins, thermoplastic elastomers (TPEs), and to some extent soft polyvinyl chloride (PVC) as well.

It is critical to use tubing specifically designed for certain applications, such as protecting light-sensitive solutions and ensuring loss-free dosage of sensitive drugs. Raumedic, for example, has developed Rausorb, Rauinert, and Rausonert to address such needs. These three application examples reflect the growing importance of multilayer extrusion in medical engineering.

Light-Sensitive Pharmaceuticals

Coextrusion and multilayer extrusion make it possible to use several different materials in a single tube, thus providing a modern, effective and, in practice, optimized solution for use in a range of medical applications. (Credit: Raumedic)

Protecting light-sensitive pharmaceuticals is crucial. Pharmaceuticals that are activated by exposure to light, or that break down in a photochemical reaction are increasingly used for special therapies. Substances like vitamin A and sodium nitroprusside take their activation energy from visible and invisible light in different ranges of wavelengths.

To provide the required protection for these substances, the development of black tubing seemed to solve the problem. This, however, makes it impossible to monitor the infusion solution. As a result, any gas bubbles, impurities, or other problems cannot be detected when they occur.

Raumedic Rausorb is designed for light-sensitive solutions. (Credit: Raumedic)

Other solutions available on the market involve transparently colored tubing, or windowed tubing made of a clear material including semi-circular segments of light-proof coextrusion materials embedded in the tubing wall. But these solutions do not comply with the applicable pharmacopoeias and relevant standards.

Raumedic Rausonert is designed for loss-free dosage of light-sensitive solutions. (Credit: Raumedic)

Multilayer tubing meets medical engineering requirements. The inner layer of this special tubing is physiologically harmless. The outer sheath is infused with light-absorbing substances that correspond to the spectrogram of each individual infusion solution. With this technology, any chosen combination of wavelengths in the 220–800 nm range can be largely filtered out. Since each preparation is only sensitive to a very specific set of wavelengths, there are enough ranges remaining to allow for the production of transparent tubing that still blocks all but a negligible amount of light in the critical wavelength ranges. This makes it possible to develop tubing that is specific to individual drugs.

Drug-Compatible Infusion Tubing

Loss-free dosage of light-sensitive solutions require specialized materials such as Raumedic’s Rauinert. (Credit: Raumedic)

For decades, soft PVC has proven its worth as an efficient and easy-to-process material for flexible infusion lines. Even today, well over 90 percent of all infusion tubing is still made from soft PVC. With advances in the development of highly effective new drugs, however, and especially in the oncology domain, an increasing number of problems have begun to arise involving drug compatibility with the PVC tubing material. Many highly sensitive drugs are adsorbed on the tubing’s surface, with the result that only a fraction of the intended dose reaches the patient.

Conversely, “undesirable side effects” may occur if plasticizers and other additives are released from the PVC material by the infusion solution. This happens most often when the infusion solution contains fatty substances or lipid-like solubilizers.

Despite these challenges, Raumedic developed Rauinert to enable the continued use of soft PVC as a safe material. The layering most commonly used with this product consists of a low-density polyethylene (LDPE) inner layer, an ethylene-vinyl-acetate-copolymer (EVA) bonding agent, and a PVC outer layer. Polyethylene is chemically neutral in contact with the flow-through medium. The EVA middle layer serves as a bonding agent between the LDPE and PVC layers, since those two materials would not otherwise form a strong bond to one another in the coextrusion process. The outer layer made of soft PVC ensures that the manufacturer of the final infusion tubing sets can conduct all of its processes just as it would with any ordinary PVC tubing. These processes include bonding, packaging, and sterilization, for example.

For drugs that are both light-sensitive and PVC-incompatible, the Rausonert tubing line offers custom-tailored solutions — with regard to the requirements of later processing steps as well. Inert inner tubing layers are coextruded with light-absorbing outer layers. The possible combinations of materials and dimensions are virtually unlimited.

PVC-Free Infusion Bags

As in food packaging technology, a trend toward the use of lightweight, flexible, and unbreakable polymeric materials is developing in containers for infusion solutions, too.

For infusion bags, the first step was the use of PVC films, tubing, and connectors containing plasticizers. Since the early 1990s, there has been an intensive search for alternative materials free of plasticizers and chlorine. For films, the industry quickly achieved adequate levels of quality that had already proven their value in the food industry. The films in question were multilayer films made from polypropylene (PP) or polyethylene/bonding agent/polyester that comply with the requirements for transparency and sterilizability with water vapor at 250 °F (121 °C).

These PVC-free film bags require special filling tubing. Whereas the outer layer should be weldable to all common films, the inner layer should provide excellent bonding to all common connector materials, such as polycarbonate, polypropylene, or hard PVC, during the steam sterilization process. Naturally, this combination of properties cannot be achieved in a single polymer formulation.

Using coextrusion technology, medical filling tubes for infusion bags can be created. This special two-layer tubing is composed of an inner layer of EVA and an outer layer made of TPE. The EVA provides excellent bonding to polycarbonate connectors, but it must be cross-linked to maintain its shape at 250 °F (121 °C).

If polypropylene connectors are preferred, three-layer tubing with a soft PP/soft PP/TPE layering can be used. With this layering, the modified polypropylene in the inner layer provides good bonding to PP injection ports, while the flexibility or stiffness of the tube as a whole can be variably controlled through the formulation of the soft PP middle layer.

Conclusion

Micro-extrusion, the coextrusion of multiple polymer layers to produce micro-dimensional tubing, has enabled the development of application-specific tubing that can be used where traditional materials can’t. Application-specific layer thicknesses, embedded color stripes, and functional layers are just a few of the characteristics that make micro-extruded, multilayer tubing a viable alternative to conventional tubing as applications become increasingly complex.

This article was written by Gert Walter, Senior Product Manager, M&S Tubing, for Raumedic, Mills River, NC. For more information, Click Here.