RADIATION STERILIZATION
Gamma and electron-beam irradiation are among the most popular and well established processes for sterilizing polymer-based medical devices. It has been long known, however, that these techniques can lead to significant alterations in the materials being treated. High-energy radiation produces ionization and excitation in polymer molecules. These energy-rich species undergo dissociation, abstraction, and addition reactions in a sequence leading to chemical stability. The stabilization process—which occurs during, immediately after, or even days, weeks, or months after irradiation—often results in physical and chemical cross-linking or chain scission. Resultant physical changes can include embrittlement, discoloration, odor generation, stiffening, softening, enhancement or reduction of chemical resistance, and an increase or decrease in melt temperature. This article discusses how and why irradiated polymeric materials change, presents data on the radiation stability of various polymers, and offers some general guidelines for material selection.
Ionizing radiation is a unique and powerful means of modifying polymers, particularly since the changes occur when materials are in a solid state, as opposed to chemical or thermal reactions carried out in hot or melted polymers. While solid-state modification may have significant advantages, any changes in material characteristics or performance brought about by radiation are governed by structure/property relationships that are perfectly analogous to those generated by other chemical and thermal processes. These include polymerization, grafting, cross-linking, changes in saturation, chain scission (degradation), oxidation, cyclization, isomerization, amorphization, and crystallization.
Many important physical or chemical properties of polymers can be modified with radiation. Among these are molecular weight, chain length, entanglement, polydispersity, branching, pendant functionality, and chain termination. Understanding how and to what extent these characteristics can be altered as a function of the level of radiation exposure (dose) is crucial to predicting the performance and utility of irradiated plastics.
The influence of radiation on the properties and performance of a polymer differs according to whether the material degrades or cross-links, and this in turn depends on specific sensitivities or susceptibilities inherent in the polymer backbone. All materials have been found to break down at very high radiation doses; however, the range of doses under which a given plastic will maintain its desirable properties depends greatly on the chemical structure of the polymer. Indeed, below the destructive level of exposure, radiation treatment can impart many benefits and enhance properties of commercial value. By gaining sufficient knowledge about these beneficial radiation-induced effects, device manufacturers can make thoughtful choices regarding polymers used in sterile medical products and ensure that critical elements of material and product performance are not compromised.
RADIATION EFFECTS
Because the effects of ionizing radiation depend greatly on polymer chemical structure, the dose necessary to produce similar significant effects in two different materials can vary from values as low as 4 kGy in polytetraflouroethylene to 4000 kGy or more in styrene or polyimide. Even the lowest doses, however, can engender significant alterations. For example, in a typical polyethylene with an average molecular weight of about 100,000 and readily soluble in a solvent such as Decalin, only one cross-link per 14,000 monomer (ethylene) units can cause gelation (insolubility).
Radiation effects on the properties of a polymer can also be difficult to predict, especially in the presence of certain additives that can help to prevent radiation damage to plastics. These compounds are frequently termed "antirads," and generally are substances that also act as antioxidants. They function either as reactants, combining readily with radiation-generated free radicals in the polymer, or as primary energy absorbers, preventing the radiation's interaction with the polymer itself.
Radiation normally affects polymers in two basic manners, both resulting from excitation or ionization of atoms. The two mechanisms are chain scission, a random rupturing of bonds, which reduces the molecular weight (i.e., strength) of the polymer, and cross-linking of polymer molecules, which results in the formation of large three-dimensional molecular networks.
Most often, both of these mechanisms occur as polymeric materials are subjected to ionizing radiation, but frequently one mechanism predominates within a specific polymer. As a result of chain scission, very-low-molecular-weight fragments, gas evolution, and unsaturated bonds may appear. Cross-linking generally results in an initial increase in tensile strength, while impact strength decreases and the polymer becomes more brittle with increased dose.
For polymers with carbon-carbon chains (backbones), it has been observed that cross-linking generally will occur if the carbons have one or more hydrogen atoms attached, whereas scission occurs at tetra-substituted carbons. Polymers containing aromatic molecules generally are much more resistant to radiation degradation than are aliphatic polymers; this is true whether or not the aromatic group is directly in the chain backbone or not. Thus, both polystyrenes, with a pendant aromatic group, and polyimides, with an aromatic group directly in the polymer backbone, are relatively resistant to high doses (>4000 kGy).
From a product use standpoint, the loss of mechanical properties is the most important characteristic effected by irradiation of polymers. These properties include tensile strength, elastic modulus, impact strength, shear strength, and elongation. Embrittlement may occur even as irradiated polymers decrease in hardness. Crystallinity and, hence, density characteristics may also change as chain scission continues.
When a polymer is subjected to irradiation by ionizing radiation—such as gamma rays, x-rays, or accelerated electrons—various effects can be expected from the ionizations that occur. The ratio of resultant recombination, cross-linking, and chain scission will vary from polymer to polymer and to some degree from part to part based on the chemical composition and morphology of the polymer, the total radiation dose absorbed, and the rate at which the dose was deposited. The ratio is also significantly affected by the residual stress processed into the part, the environment present during irradiation (especially the presence or absence of oxygen), and the postirradiation storage environment (temperature and oxygen).
EFFECTS OF OXYGEN AND DOSE RATE
The environmental conditions under which radiation processing is conducted can significantly affect the properties of the polymer material. For example, the presence of oxygen or air during irradiation produces free radicals that are often rapidly converted to peroxidic radicals. The fate of these radicals depends on the nature of the irradiated polymer, the presence of additives, and other parameters such as temperature, total dose, dose rate, and sample size. A variation in processing conditions in the presence of polymer additives can result in gas evolution and formation of other degradation products from these small molecules, with the possibility of producing irritants or other undesirable compounds.
A significant difference in irradiation processing exists between electron-beam and gamma sterilization related to dose rate and, ultimately, to the oxidation degradation of material at or near the surface. Dose rate refers to how fast energy is absorbed and depends on many factors including the source, strength, and size of the radiation field; its distance from the source; and the type of radiation. For electron and gamma sources of the same strength, the dose rate of the electron source is many times greater than that of the gamma source. This is because the electron beam is unidirectional and is concentrated in a much smaller region, and because the interaction of electrons with other electrons is much stronger than with photons.
Although the difference may be minute, it can be said in an absolute sense that all polymeric materials undergo less material embrittlement in electron-beam than in gamma-ray sterilization as a result of reduced oxidative chain scission. For many products, this is not critical, but is important to keep in mind when selecting a radiation sterilization process for oxidation-sensitive materials such as polypropylene, nylon, or Teflon or for products containing thin profiles, such as films and fibers.
Additional explanation will help clarify this phenomenon. As a polymer is irradiated, radicals are formed in a concentration proportional to the local dose. However, the associated stabilizing chemical reactions that follow are proportional to the local concentrations of reactants. Because the concentration of reactants differs by location (i.e., higher oxygen near exterior surfaces), the resultant radio-chemical stabilizing reactions are thus heterogeneous.
In both gamma and electron-beam irradiation systems, available oxygen is quickly consumed within the polymer. However, in the case of electron-beam processing, the time of energy application is so short that before more oxygen can permeate into the material from its external surfaces, the application of radiant energy has been terminated, the direct formation of additional radicals ceases, and the stabilizing chemistry pursues alternate, less-degrading routes (recombination or cross-linking). In simple terms, the chemistry changes as a result of a starved chemical reaction—much as a fire goes out when the oxygen is consumed in a closed container. In gamma irradiation, the application of ionizing energy continues over a much longer period of time, allowing reactants, such as oxygen, to permeate back into depleted areas of the material, resulting in a greater degree of chain scission.
COLOR AND ODOR
A common undesirable effect resulting from the irradiation of some polymers is discoloration (usually yellowing) from the development of specific chromophores or color centers in the polymer. Color development, which occurs at widely differing doses in various polymers, may diminish or increase with storage time after irradiation. Often, discoloration appears prior to any measurable loss in physical properties. Such as is the case, for example, with PVC, in which radiation-induced yellowing from conjugated double bonds develops at a dose much lower than is necessary to cause any reduction in the material's physical properties.
Another problematic effect in some polymers that results from specific radio-stabilizing chemistries is odor. The polymers that most commonly exhibit post-irradiation odor are polyethylene, PVC (rancid oil odor from oxidized soybean and linseed oils in the plasticizer), and polyurethane.
If the reaction chemistries causing the odors are understood they can often be mitigated through the use of antioxidants, different processing temperatures, or selection of a higher-molecular-weight polymer. Odor reduction can also be accomplished through the use of gas-permeable packaging (for example, Tyvek, paper) and elevated temperature conditioning.
MATERIAL SELECTION
In addition to personal experience, materials databases, supplier information, and literature searches can be used to help avoid potential problems with polymers that are less radiation resistant than required for a particular product's design and function. Material selection should be done with diligence, especially when dealing with thin sections such as films, coatings, and fibers as well as with materials having low radiation resistance such as acetal, polypropylene, or Teflon (these three polymers can be remembered as those that are "APT" to fail). It must be remembered that the physical properties of irradiated polymers are subject to significant variations due to residual or functional stress, section thickness, molecular weight, morphology, moisture, and storage environment (oxygen/temperature), and must be tested in the specific application under consideration.
The selection of materials for radiation sterilization should start with the following basic rules:
- Most medical plastics are durable in radiation.
- Use the highest-molecular-weight material (with the narrowest molecular-weight distribution) that is possible for the application.
- Aromatic materials are more radiation resistant than are aliphatic materials.
- Amorphous materials are more radiation resistant than are semicrystalline materials.
- Higher levels of antioxidants improve radiation resistance.
- Low-density materials are more radiation resistant than high-density materials.
- Materials with small pendant (side) groups are more radiation resistant.
- For semicrystalline materials, the lower the crystallinity, the greater the radiation resistance.
- Materials with low oxygen permeability are more radiation resistant.
- Avoid materials that are "APT" to fail: acetal, polypropylene (unstabilized), or Teflon (PTFE).
Information derived from government, industrial, and scientific studies and publications concerning radiation effects on polymer properties after exposure to various doses is summarized in Figures 1 [6] and 2 [7], which graphically display the dose at which a number of common thermoplastics and thermosets experience a 25% loss in elongation. (Loss of elongation is a commonly used measure of the effect of irradiation.) These figures provide a visual means of making an initial estimate of a polymer's ability to withstand a typical sterilization dose (10–50 kGy) or a higher dose used in a more specialized radiation process. A more qualitative summary of the radiation stability of selected polymeric materials is provided in Table I [8].
CONCLUSION
When used to enhance polymer properties or to sterilize polymer-based medical products, ionizing radiation interacts with polymers via two primary mechanisms: chain scission to reduce molecular weight and cross-linking to generate large polymer networks. Both mechanisms occur in all polymers during irradiation, but one generally dominates. Polymers vary in sensitivity to radiation from PTFE and polyacetal, with damage occurring at doses as low as 4 kGy, to polystyrenes, polyimides, and LCP, which can tolerate doses as high as 105 kGy without significant damage.
Polymers containing aromatic groups have much greater resistance to radiation damage than those with aliphatic structure. Most thermoplastics, essentially all thermosets, and most elastomers can withstand at least one radiation sterilization (<50 kGy) without significant damage. Because of oxidative effects, polymeric materials used in adhesives, fibers, films, and encapsulates show slightly lower radiation tolerance compared with bulk polymers; however, the use of antioxidant additives can significantly offset the effects of radiation.
With a basic understanding of the effects of radiation on polymers, reference data available from polymer manufacturers and other sources, and a thorough understanding of the product's manufacturing process and intended use, wise choices of radiation-tolerant materials can be made for the majority of medical product applications.
REFERENCES
1. Information sources include polymer manufacturers' data; "Effects of Radiation on Polymers & Elastomers," NASA/Jet Propulsion Laboratories, 1988; Skeins and Williams, "Ionizing Radiation Effect on Selected Biomedical Polymers"; Kiang, "Effect of Gamma Irradiation on Elastomeric Closures," Technical report 16, PDA, 1992; Ley, "The Effects of Irradiation on Packaging Materials," 1976.
2. Some information derived from IAEA, 1990.
Karl J. Hemmerich is general manager and corporate technical advisor at Isomedix Corp.'s gamma irradiation facility located in Sandy, UT. He was formerly president of Ageless Processing Technologies, a consulting firm specializing in the medical disposables market, and has also worked at Ivac Corp., Cutter Laboratories, and Becton Dickinson. He was a member of the task force that developed the technical information report for postirradiation of materials (ISO 11137).
Photo by Roni Ramos