Medical Device Link.

Advancing the extrusion process

The primary aim of coextrusion technology, leaving aside any commercial considerations, is to improve the functionality of tubing products. The resulting benefits such as increased design possibilities, a combination of multiple polymer materials and thereby the integration of additional functions, and the reduction of secondary fabrication and assembly processes makes the technology interesting. Coextrusion can be defined as the extrusion of multiple (three to four) layers of material simultaneously to give multilayered tube. Micro extrusion, discussed below, is the extrusion of micro tubes with diameters smaller than 1 mm. This article explains how both extrusion processes can be combined to good effect.

Multilayer and micro extrusion

Multilayer extrusion in the area of film production no longer represents a significant challenge to machinery and tool technology; however, the coextrusion of multiple polymer layers in the production of small dimensional tubing is in many cases still a relatively new process for engineers. It is now possible to produce on special micro extrusion lines multilayer tubing for different applications with up to three different polymer materials. With this technique, the smallest possible inner tube diameters are approximately 0.1 mm (100 µm) with wall thicknesses in the order of 0.05 mm (50 µm). The micro extruders used for this can work with throughput rates of as little as 50 g/h flow rate.

In principle, the range of polymers feasible for use in coextrusion is unlimited. However, of particular interest are those thermoplastics that have long established use in health care applications. These include thermoplastic polyurethanes, polyamides, polyolefines, thermoplastic elastomers and plasticised poly(vinyl chloride) (PVC). High temperature thermoplastics such as polyetherimide or polyetheretherketone are also suitable for processing by micro extrusion; these materials are regarded as replacements for metallic materials because of their superior mechanical properties.

There is a multitude of potential applications, but the following four developments illustrate the growing significance of coextrusion and micro extrusion in medical device technology.

Infusion therapy

Drug compatible infusion tubing for sensitive active ingredients typically employs soft plasticised PVC. This is a low cost, easily processable material that has proven use over many decades, thus it is the material of choice for flexible infusion lines. In particular, the relatively simple process of solvent bonding PVC to other polymer components in tube sets and its convenient properties for sterilisation have supported PVC’s dominance in this area. Even today more than 90% of all infusion tubing continues to be produced from plasticised PVC.

However, the development of highly efficacious drugs, particularly for oncology, brings with it increasing problems concerning the compatibility of active ingredients with PVC tubing. Many sensitive substances such as insulin, nitro glycerine and cytostatic cancer drugs are adsorbed at the surface of PVC tubing with the effect that only a portion of the desired dose reaches the patient. The loss of active ingredient is a well known problem, but one that frequently receives little attention in clinical practice.

At the other extreme, undesired side effects are caused by the opposite effect; that is, in many cases the infusion solution can dissolve considerable amounts of plasticiser and other PVC additives, which end up inside the patient. This happens particularly when the infusion solution contains fatty substances or lipid-like solubilisers that can absorb with ease plasticisers from PVC.

Multilayer tubing overcomes the problem of adsorption. The most commonly used layer structure employs an inner low density polyethylene (LDPE) layer, an ethylene vinyl acetate (EVA) tie layer and an outer layer of PVC (Figure 1). LDPE is completely neutral on contact with the flow medium; it neither leads to loss of active ingredients through adsorption of substances from the solution, nor to contamination of the infusion solution with migrating substances from the polymer material. The EVA layer serves as a bonding layer between LDPE and PVC; without this layer these two materials would not achieve a firm bond to each other in coextrusion. The plasticised PVC outer layer ensures that the fabricator of the finished infusion tube set can perform all the necessary processes such as bonding, packaging and sterilisation just as with a standard PVC tube. The growing awareness amongst pharmaceutical manufacturers and clinical users of the problem of incompatibility between infusion solution and tubing material is sure to drive further growth of this highly specialised multilayer tubing for infusion therapy.

Regional anaesthesia

Specialised regional anaesthesia, commonly used, for example, in orthopaedic surgery, eliminates the risks and unpleasant effects of total anaesthesia. With this method, a small catheter tube is inserted via a tiny metal cannula into the nerve channel in the spine (spinal channel). By injecting the local anaesthetic into a specific point within the spinal channel, anaesthetisation of all body parts below this point is achieved while the patient remains fully conscious throughout the surgery.

The demands on the catheter material are wide ranging. The tube must have extremely small dimensions, for example, 0.35 x 0.6 m, and be flexible enough not to damage any nerves within the spinal cord. It must also have particularly good kink resistance, 15–35 mN, so that it can negotiate the tight radii between the spinal vertebrae when the tube is inserted. It is vital that the tube does not kink during this process, because it would lead to an interruption of the anaesthetic supply. Furthermore, the tube needs a high level of transparency to allow the fluid in the inner lumen to be visually checked. Of course, other parameters such as suitability for sterilisation and biocompatibility must also be observed.

These requirements are achieved with a two-layer tubing consisting of a polyamide inner layer and a polyurethane outer layer. These materials achieve a firm, permanent bond with each other during the coextrusion process. The unique approach of this material combination means that the polyamide layer is responsible for the mechanical strength of the tube, in particular its kink resistance. Length markers can be easily printed on the polyurethane and the material has good biocompatibility in contact with body fluids and tissue.

A particular challenge for engineers working on this catheter was the extrusion of X-ray contrast stripes, which had to be embedded in the tube wall. The diameter of these stripes filled with X-ray contrast agent is 0.04 mm (40 µm), that is, less than half the width of a human hair (approximately 100 µm). The construction of appropriate extrusion tools is an extreme challenge for precision engineering.

Two-lumen tubing for micro dialysis

Micro dialysis opens up new opportunities in the continuous quantitative analysis of blood solutes. With this method it is no longer necessary to take blood samples from patients. Instead, the substances to be measured can diffuse out of the blood via a thin membrane (hollow fibre) and are then measured using common analytical methods. The rinsing solution is usually a physiological saline solution. Diffusion of blood solutes is achieved just like in dialysis as a result of osmotic pressure until a concentration equilibrium is achieved between the blood and the rinsing solution.

The technical solution consists of a two-lumen catheter fabricated from polyamide or polyurethane into which are cut small window segments to give access to a dialysis membrane. The catheter is U-shaped, which means that the flow of the rinsing solution is “cut short” at the tip and the saline solution is returned to the analysis equipment after taking up the solutes to be analysed. This makes continuous measurement possible without the need to take large quantities of blood samples from the patient. The micro catheter is inserted via a typical intravenous cannula (Figure 2).

Parenteral feeding

Life support of premature babies (neonates) is an excellent example of progress in medicine and medical technology over the past few decades. Only a few years ago, these neonates had low survival rates, but through optimised enteral feed therapy and ventilation systems many children are now saved and start a completely normal life without physical disability. Medical technology has played a big role in this.

Some manufacturers have specialised in the manufacture of products in the smallest dimensions for the treatment of small children. Children’s veins are so small and delicate that conventional catheters would be completely unsuitable. As an example, Figure 3 shows a polyurethane catheter with X-ray contrast stripes in size 24 gauge, which is typically used for intravenous cannulae. The tube wall has a width of 0.1 mm.

Further developments

Micro extrusion technology and multi-layer coextrusion offer new opportunities for manufacturing novel medical devices with even smaller dimensions than current products. Other developments can be expected in the near future such as coextruded tubing with thin metal wires so that the tubing can be employed as a data transmitter.