Originally published September 1996
Most current medical plastics applications feature materials that have been compounded in some fashion to optimize their performance. For example, polyvinyl chloride (PVC) typically used in medical fabrication often contains 10 or more ingredients, among them stabilizers, antioxidants, and other additives. Most engineering resins are compounded with UV stabilizers, processing aids, and reinforcing agents
such as glass fibers. Thermoplastic elastomers, alloys, and blends are normally compounded in order to make up the standard grades. The compounds that result--so familiar as to be sometimes thought of as off-the-shelf resins--are what device manufacturers and processors use to satisfy the requirements of most medical applications.
Despite the availability of thousands of grades derived from dozens of plastic resins, medical product designers continue to develop new, application-specific specialty compounds. This article offers a general overview of the compounding process and describes some of the most commonly employed fillers and additives, in the hope that a basic understanding of compound materials will help facilitate timely, cost-effective product development. Although the information presented should be helpful in the production of any polymer-based device, the discussion is particularly geared toward compounds for catheters and other medical tubing products.
Depending on the precise application, a typical starting resin might be PVC, thermoplastic polyurethane, polyether block amide elastomer (PEBA), flexible nylon, polyethylene, styrenic block copolymer, or fluoropolymer. It is important to select a base resin or family that has most of the attributes required in the finished compound. For instance, if high tensile strength is called for in a semiflexible compound, PEBA resin may be selected. Many times, the various grades within a resin family can be melt compounded to provide intermediate properties more specific to the application. Reactive compounding, grafting, and compatibilizing of blends can also be achieved. Though very exciting, the creation of new compounds through reactive compounding is also an extremely involved process, given the virtually unlimited number of options. This topic alone could be the focus of another article.
The basic premise of effective compounding is first to incorporate an end product's functional requirements--for example, radiopacity, color, or lubricity--and then to fine-tune the formulation and compounding process to obtain optimum results. Of course, any discussion involving specific materials for medical applications is based on the understanding that the device manufacturer is ultimately responsible for all testing--including material testing--to satisfy regulatory requirements.
In order for a plastic to be visible under fluoroscopy, it must contain a certain amount of radiopaque filler. The type and amount selected depend on the base resin and on the size (thickness), surface smoothness, color, and desired properties of the finished device. Although numerous metals and other materials have been evaluated as radiopaque fillers, 90% of all compounds use one or more of the five substances discussed below to promote radiopacity (see Table I).
Barium Sulfate. Low in cost and very stable, barium sulfate is the most commonly used radiopaque filler. The preferred form of barium sulfate is a white powder, with particle size ranging from 0.5 to 2 µm. Some grades may appear light gray or brown, but these often require high-temperature predrying to drive out residual volatiles left over from the manufacturing process, and are best avoided if possible.
Barium sulfate can be incorporated into thermoplastic elastomers up to 60% by weight without a significant decline in properties; semicrystalline resins such as nylon 12 and polyethylene can tolerate a 40% loading. Amorphous resins--for example, polycarbonate--cannot be filled as high. Although white barium sulfate can be used as a pigment, its poor tinting strength means that high loading is required to make the plastic opaque in thin sections. The same poor tinting strength can be an advantage, however, when coloring compounds, making it possible to obtain a wide color range, including dark colors and black, when barium is used as the radiopaque medium. All grades of barium sulfate used in medical devices should meet the relevant requirements of the United States Pharmacopeia (USP).
Bismuth Subcarbonate. After barium sulfate, the most popular radiopaque filler is bismuth subcarbonate. Because of its instability at temperatures around 400°F, bismuth is a bit more challenging to compound than barium sulfate. It also may not be compatible with all resins: for example, some polyurethanes may depolymerize during compounding when bismuth is added. Though more stable grades are currently being developed, bismuth fillers are still not often used with many polyurethanes, especially aromatic polyether urethanes.
Bismuth is denser than barium sulfate, and is recommended when more radiopacity is required. Higher density means that an equal weight percentage of barium and bismuth translates to a lower volume percentage of bismuth. Bismuth can thus be used at relatively high loadings--30 to 50% by weight--with little effect on polymer physical properties.
For the better grades of bismuth fillers, particle size ranges from 1 to 2 µm. The powder is white and fluffy and, depending on the grade, can be difficult to feed into an extruder because of low powder-bulk densities--a problem that can be overcome with proper compounding techniques. Bismuth is a strong white pigment, difficult to color match. It also has a tendency to turn yellow (reducing to bismuth trioxide) when compounded, which again makes it hard to maintain consistent color from lot to lot. Dark colors are not possible with bismuth subcarbonate. In general, good bismuth compounds require careful control over the entire compounding process, including precise temperature control of the extruder. Once again, USP grades are required for all medical applications.
Bismuth Trioxide. Like bismuth subcarbonate, bismuth trioxide is very dense and makes an excellent radiopaque filler. Its major drawback is its yellow color. If processed too hot, bismuth trioxide compounds turn brown, which has little if any effect on compound properties but is often undesirable for aesthetic reasons. Trioxide has a very high bulk density and is easy to feed. Gritty surfaces are occasionally a problem, but can sometimes be corrected through melt filtering. Bismuth trioxide is generally recommended if a high level of filler is required--for example, 60% by weight--or if bismuth subcarbonate cannot be compounded satisfactorily in a particular resin.
Bismuth Oxychloride. A white powder with a soft, silky feel, bismuth oxychloride is more temperature-stable than bismuth subcarbonate and is compatible with a wide range of resins. Particle size is typically from 2 to 12 µm; particles have a platelet structure that aligns during processing to form a smooth, shiny surface. Bismuth oxychloride is susceptible to UV degradation, and therefore requires addition of a UV stabilizer to combat this effect. Coloring properties are similar to those achieved with bismuth subcarbonate, with some grades producing a pearlescent appearance.
Tungsten. A very heavy metal powder compatible with virtually all resins, tungsten provides high radiopacity. Loadings up to 90% by weight are typical. The best grades have particles measuring between 1 and 2 µm, with low impurities. Tungsten compounds often show a characteristic matte finish at high loadings, and are dark gray in color. Because tungsten is so abrasive, it can wear out mixing elements in just a few weeks. Pelletizer bed knives and rotors will also wear rapidly, and extruder screws running tungsten compounds should be inspected frequently.
Colored compounds require formulation with pigments or dyes. It is generally advisable to employ the least amount of colorants in the formulation as possible; a good rule of thumb is to use less than 1% by weight. Although color concentrates have been used in many applications with success, it is more difficult to formulate using concentrates because they may contain unknown ingredients; in several cases, problems with a compound have been attributed to the improper use of concentrates. If possible, it is best to avoid concentrates if one is developing a new catheter compound.
In color matching, it is important to understand the limitations of the base resin and any other ingredients and to realize that a perfect match may not be possible. The Pantone color-chart system is commonly used, but the colored plastic will almost never exactly match the colored paper sample. A computerized color-matching system with a database comprising medically approved pigments and compounds can significantly speed up the matching process. As is the case with other additives or fillers, there are thousands of colors to choose from, and color qualification for medical applications is a time-consuming, expensive process. It is always best to use a pigment that has performed well in similar applications and with similar resins. As always, thorough testing of the finished device is essential when validating any new compound.
Titanium Dioxide. The most versatile pigment is titanium dioxide, a strong, white powder pigment that gives a uniform, opaque white color at 1% loading by weight and is also used in combination with other pigments to obtain most colors. Though compatible with all radiopaque fillers, titanium dioxide will not, however, overcome the yellowing of bismuth compounds. The rutile type is most often selected, and grades with very low impurities are required for medical compounds; special grades may be employed to reduce brittleness when added to polycarbonate and other amorphous engineering resins.
Organic Pigments. Phthalocyanine blues and greens in various shades are among the more common organic pigments. These colorants are particularly strong, and a loading by weight of 0.1% is usually sufficient to produce a mid-tone color. Phthalocyanine pigments are temperature stable up to about 450°F; the reducing nature of nylons will often turn a green to blue if the compound is processed at higher temperatures. Quinaridone red and violet--also very strong organic pigments that are compatible with most resins--are stable up to about 500°F.
Produced through a natural gas process, channel blacks are a carbonaceous soot that acts as a strong black pigment with excellent heat stability when used in weight concentrations up to 0.5%. Carbon black is also a carbonaceous soot, but is manufactured by a furnace process. A low-impurity, low-sulfur grade is required for medical applications. Both carbon and channel blacks help improve the UV stability of a compound.
Dyes are organic compounds that are soluble in many plastics. These colorants are suitable for some transparent compounds and can be compounded in at very low concentrations of less than 0.1%. Because dyes are soluble, migration is potentially a concern, and dyes should always be evaluated with the specific resin they are intended to color.
FD&C colors--also called lake pigments or food colorants--are composed of a dye chelated with an inorganic substrate, usually aluminum hydrate. Lake pigments typically contain only 20 to 40% pure dye and therefore must be added in sufficient quantity to achieve a satisfactory depth of color. Although lake pigments, being nontoxic, are excellent for food packaging applications, they are soluble in water and have a tendency to bleed out of some resins. FD&C red and yellow have been used successfully at about 0.5% weight loading. These pigments also contain between 20 and 30% moisture, and must be dried before use. Lot-to-lot variation in dye content requires the compounder to color match each new lot for critical colors; manufacturers specifying these pigments should always design in a generous tolerance to allow for this fluctuation.
Inorganic Pigments. Useful inorganic pigments include ultramarines and iron oxides. Available in several different shades of blue and violet, ultramarines offer better temperature resistance than do organics. However, they are relatively weak, and may also discolor in acidic conditions.
Iron oxides are essentially a form of rust that comes in black, brown, and red. They have good heat stability, and the clean, cosmetic grades have been used successfully in many resins. Tinting strength is moderate, but much lower than that of carbon black. Small amounts used in combination with other pigments help to achieve a wide range of colors. Higher loadings of iron oxides on dark colors tend to produce a matte finish in some resins.
As with all additives, device manufacturers should verify that pigment suppliers follow GMPs so as to ensure the good quality and low level of impurities critical for acceptance in medical compounds.
OTHER COMMON ADDITIVES
Depending on the base polymer family and the level of additives already contained in the starting resin, a compound may require additional ingredients such as heat and light stabilizers, antioxidants, processing aids, or lubricants. Other common additives include plasticizers, cross-linking agents, coupling agents, reinforcements, nucleating agents, and conductive additives.1
Heat Stabilizers. Typically required for PVC formulations, the addition of heat stabilizers is generally not necessary for other resins.
Antioxidants. Additional antioxidants can be important for resins that are very susceptible to degradation during processing or that lose properties rapidly upon aging. Urethanes, for example, often benefit from additional antioxidants. Careful antioxidant selection is required to prevent blooming to the surface due to incompatibility. For medical compounds, the toxicological properties of the additive are of primary concern: the lower the level of antioxidant used, the better, and as little as 0.3% or less of some antioxidants has been employed successfully.
Ultraviolet (UV) Stabilizers. It is sometimes necessary to give a compound longer-term protection against degradation in the presence of light. Elastomers containing polyether segments, for example, are susceptible to UV degradation and may require a UV additive. The selection process is similar to that for antioxidants.
Processing Aids. Processing aids are designed to impart internal or external lubrication to a compound. Types of processing aids include fatty-acid esters, such as glycerol monostearate; fatty-acid amides, such as bisstearamides; waxes; oxidized polyethylene; and others. A small percentage of fluoropolymer or silicone is also sometimes added as a processing aid. These ingredients can reduce process degradation, enhance mold-release action, aid in the dispersion of minor ingredients, and help produce a slicker surface on an extruded or molded part. Migration of these additives can be a concern, however, along with adverse effects on secondary processes such as bonding. Several nontoxic and FDA-compliant grades have been used successfully in medical applications.
Lubricants. Improvements in the surface lubricity and wear resistance of polymer compounds can be accomplished with lubricants such as PTFE or silicone. PTFE powder has a very low coefficient of friction, and its uniform incorporation into a base plastic enables the PTFE particles at the surface to provide lubrication. PTFE is typically added at between 2 and 20% by weight. Particle size is important and should be matched to the application: the surface of extrusions containing PTFE is sometimes rough, depending on the particle size used.
Silicone is a lubricious fluid, added at loadings of between 0.25 and 2% by weight, that migrates to the surface of a plastic and provides lubrication. Care must be taken to use the proper amount, as too much silicone can make a compound hard to feed into an extruder and may also give the component an oily feel.
Silicone and PTFE work well together, and some of the best frictional properties are obtained from this combination. Graphite and molybdenum powders have also been used (at between 0.2 and 0.5%) as lubricants, and have the effect of coloring a compound medium to dark gray. Molybdenum is added primarily to nylon, since it also nucleates (crystallizes) the resin surface, improving lubricity.
BLENDING AND COMPOUNDING
For some standard applications, incorporating fillers, colors, and other additives into a resin can be as easy as preblending all the ingredients together and loading them into a single-screw extruder hopper for strand pelletizing. As requirements become more stringent--the case for many medical projects--the compounding becomes more interesting, involved, and specialized.
Many types of compounding machines and mixers are available, and satisfactory compounds can be produced on most of them. While individual operator preference plays a major role, certain machines are more flexible and do a better job than others on specific compounds.
Melt Compounding. Procedures for melt compounding encompass two kinds of mixing, distributive and dispersive. For example, when fibers are incorporated into a resin, good distribution is required without breaking down the fiber segments: this is characteristic of distributive mixing, a relatively gentle homogenization of the material. Dispersive mixing is associated with the breaking up of agglomerates and generally correlates to high strain and shear rates.
Machines capable of both distributive and dispersive mixing include Banbury-type batch mixers, Farrel continuous mixers, and twin-screw extruders. The twin-screw extruder offers the most flexibility, since the barrel length and screw configurations are adjustable. Downstream oil injection and powder or fiber feeding is also possible.
Pelletizing. For materials with good melt strength that are not too soft and tacky, strand pelletizing is preferred. With this method, the pellets are cylinder-shaped and have a diameter of approximately 0.1 in. and a length of 0.125 in. Strand-pelletized compounds feed well on virtually all extruders. Soft and sticky compounds are usually underwater pelletized: the pellets are cut at the die face in a water chamber, conveyed in a pipe with the water, and then separated in a centrifugal dryer. Pellets are typically football shaped or round, with a diameter of 0.1 in. Micropellets with diameters as small as 0.02 in. can be produced by underwater pelletization, but are generally not recommended for medical compounds because the micropellet dies tend to restrict flow and feed rate, causing degradation in sensitive compounds. Small pellets of about 0.06-in. diam can be produced with a special die that prevents such degradation; these pellets will extrude on the smallest of machines.
Compound Development. The stages of a typical compound-development project will follow a flowchart similar to that shown in Figure 1. Once the need for a new compound is determined, a development team is assembled and the compound requirements are defined. A project plan should include enough time to research existing designs and databases and to determine starting formulations. Acquiring raw materials can necessitate a lead time as long as 2 to 4 weeks. If possible, it is advantageous to schedule compounding time in advance so that materials can be compounded soon after they arrive.
Processing and physical testing come next: several iterations may be required to fine-tune both the formula and the compounding process. When the ingredients are firmly established, biocompatibility testing can begin. Several lots of compound should be produced in order to isolate the effect of control variables such as melt flow and to determine the repeatability and capability of the compounding process.
Once it is verified that the compound meets specified requirements, a production prototype run should be made and final product fabricated. Final validation should include complete biocompatibility testing, physical testing, and field testing. If the validation is successful, a formal specification is written for the compound and a product code assigned.
Specialty plastic compounds are used in many medical devices for which a standard grade of material cannot meet all the specifications of an application. When developing a medical compound, it is always best to select ingredients and processes that have functioned well in the past in order to save time and money. The successful development of new specialty plastic compounds that satisfy the requirements of today's innovative medical designs represents a continual challenge for both device manufacturers and compounders.
1. Gachter R, and Muller H, Plastics Additives, 3rd ed, Munich, Germany, Carl Hanser Verlag, 1990. This source contains detailed descriptions of a wide range of additives.
Larry Acquarulo is president of Foster Corp. (Dayville, CT), a supplier of custom thermoplastics, elastomers, and blends. He holds a BS in plastics engineering from the University of Massachusetts Lowell and an MS in materials science from the University of Connecticut.