Silicone rubber is widely used in the pharmaceutical industry, where sterilizability is an essential requirement for all fluid transfer equipment. Pharmaceutical products are sterilized frequently and repeatedly by high-level energy and/or chemical vapor to eliminate bacterial surface contamination. Such treatments may also affect the molecular structure of silicone rubbers, causing changes in their physical properties and performance. Several studies on this topic have been reported; until now, however, no systematic investigation has been performed on the effect of standard sterilization procedures on commonly used commercial silicone rubbers. Most investigations have focused on the treatment of unfilled silicone polymer under ideal radiation conditions, the results of which cannot be directly correlated with the effects of realistic sterilization conditions on commercial tubing, hose, and connection components. This report can serve as a material selection guide for process engineers working in pharmaceutical manufacturing facilities as well as a tool for selecting sterilization procedures that are compatible with specific tubing and hose products.

Three common sterilization techniques were applied to three commercially available silicone rubbers: gamma-ionizing irradiation, electron-beam irradiation, and ethylene oxide (EtO) treatment. We investigated their effects on the mechanical properties of platinum-cured liquid silicone rubber (LSR), platinum-cured high-consistency rubber (platinum-cured HCR), and peroxide-cured high- consistency rubber (peroxide-cured HCR). Our results provide a complete picture of the effects of sterilization on the physical properties of silicone rubbers typically used in the pharmaceutical industry. This information is key to ensuring that, irrespective of repeated sterilization cycles, functionality provided by silicone parts is maintained throughout a product lifecycle.

Sterilization Techniques and Their Effects

The most common methods used for sterilizing pharmaceutical tubing and hoses are autoclaving (steam sterilization), ethylene oxide (EtO) gas treatment, and gamma or electron-beam (e-beam) ionizing irradiation (1).

Gamma radiation is known to induce changes in the molecular architecture of silicone rubber, increasing its molecular weight and decreasing elasticity. The effect is also observed in samples previously subjected to postcure treatments. Radicals are generated by chain scission and/or methyl or hydrogen abstraction, and they are subsequently terminated by oxidation reactions or coupled to form longer chain branches (Figure 1). Those two mechanisms compete against each other, but crosslinking reactions dominate in silicone materials. Higher dosages of gamma radiation and longer treatment cycles have been shown to cause higher crosslink densities (2). An increase in polymer–filler interfacial interactions through crosslinking reactions is also observed. A 2008 review by Clarson et al. describes the behavior of various silicone polymers upon exposure to gamma radiation (3).

Interaction of gamma radiation or electrons with matter generates a shower of secondary electrons that initiate ionization and induce free radicals in polymers (4). As a result, gamma and electron irradiation produce scission and crosslinking reactions. Electron radiation also modifies the polymer–filler interface, contributing to the development of physical and chemical crosslinking in the rubber and increasing its durometer hardness and tensile modulus (5).

Although gamma radiation has about five times the penetration capability of e-beam radiation (Figure 2), electron-beam sterilization can take less than a minute to reach the required dose, whereas gamma irradiation delivers the same sterilizing dose over several hours (6). Because of that shorter exposure time, the possibility of oxidative degradation (free radicals reacting with oxygen) may be decreased with e-beam sterilization if a procedure is performed in air. Ultimately two sterilization condition-dependent phenomena will affect the crosslink density of silicone resins: an atmosphere-dependent availability of unconsumed radicals that can participate in crosslinking reactions and an exposure time–dependent quantity of chain-scission reactions that occur (7). Overall, the effect of electron-beam and gamma sterilizations on the mechanical properties of silicone rubbers is expected to be similar.

Ambient temperature sterilization methods are sometimes preferred over conventional dry heat, irradiation, or autoclaving because high temperatures can extract of low–molecular-weight species from the sterilized material. One such method is EtO gaseous sterilization, which is effective in eliminating bacteria at the surface of silicone fluid transfer devices. It can present potential toxicological issues, however, if the gas is absorbed into and subsequently released from a component into tissue. Several studies have addressed this issue by quantifying the speed of absorption and desorption of EtO for silicones (8,9). To the best of our knowledge, the effect of EtO sterilization on the mechanical properties of silicone remains unknown.

Experimental

Materials: The Elastosil LR3003/50 LSR used in this study was obtained from Wacker Chemie AG (www.wacker.com). The Elastosil R4000/50 platinum-cured HCR used in this study also came from Wacker. HV3 622 base-rubber peroxide-cured HCR was obtained from GE Bayer Silicones GmbH & Co. KG (www.gesilicones.com). It was cured by Di-2,4-dichlorobenzoylperoxide with 1% loading.

Sterilization By Gamma Exposure: Three levels of gamma irradiation experiments were performed in air on the three silicone rubbers by STERIS Isomedix Services using 60 Co as a radiation source. The dosing levels of gamma radiation were 25, 50, and 75 kGy.

Sterilization By E-beam Exposure: Three levels of e-beam irradiation experiments were performed in air on the three silicone rubbers by STERIS Isomedix Services using an 80-kW 5-MeV system electron beam. Dosing levels were 10, 40, and 80 kGy.

Sterilization By EtO Treatment: The three silicone rubbers were exposed to 100% ethylene oxide at room temperature in a fully automated conveyor system at the STERIS Isomedix Services facility in Spartanburg, SC.

Mechanical Testing: We evaluated tensile, modulus, and elongation properties on an Instron material testing machine using the ASTM D-412 standard. Tear tests were performed on the same machine according to the ASTM D-624 standard. Hardness measurements were carried out on a Shore A durometer from Rex Gauge Co. (www.rexgauge.com), following the ASTM D-2240 procedure, and measured in “shA” units. Each data point reported on the plots in Figures Figures 318 is an average of five specimens from the same sample.

Results and Discussion

Effect of Gamma Irradiation: As the gamma radiation dose increases, the hardness and modulus of silicone rubber also increase because they are directly proportional to the crosslink density of the rubber. In our study, hardness (increase by >10 shA after 75-kGy radiation) and modulus (>200% increment after 75-kGy radiation) of the peroxide-cured HCR were most affected by gamma radiation (Figures 3 and 4). This can be explained by the presence of radiation-sensitive oxygen-containing active species in peroxide cured silicone rubbers that promote the formation of free radicals, resulting in increased chain branching. The hardness and modulus of platinum cured LSR and HCRs increase slightly upon gamma radiation exposure, possibly due to unreacted SiH functionalities inducing further crosslinking. The slight initial drop (after 25 kGy gamma radiation) in the durometer hardness and the tensile modulus of the platinum cured HCR may be attributed to a disruption of the hydrogen bonds on the filler surface (10). This behavior has also been observed by Patel et al. (11).

Unsurprisingly, gamma radiation reduced the tensile elongation of each of the three silicone rubbers tested, as illustrated in Figure 5. Property degradation of the peroxide cured rubber was more extensive, with up to 75% reduction in tensile elongation occurring after exposure to a 75 kGy dose of gamma radiation. Only 45% and 35% reductions in tensile elongation were observed at the same radiation dose for platinum cured LSR and HCR, respectively.

The effect of gamma radiation on tensile strength is mostly due to the silicone rubber filler content and treatment (proprietary information for the commercially available materials evaluated during this study). So it is difficult to predict or rationally explain the data trend plotted in Figure 6 We observed that gamma radiation had a minimal effect on the tensile strength of LSR and platinum-cured HCR. By contrast, the tensile strength of the peroxide-cured HCR was reduced by 50% after the sample was exposed to a 75-kGy dose of radiation.

Tear strength is primarily affected by the arrangement of crosslinking, bimodality (ratio of short polymer chains to long chains), and the amount of crosslinker used for curing rather than by the crosslink density itself. It is also well known that the tear properties of silicone rubber are dictated by the amount and type of filler used (11). Again, information on the content and nature of fillers is unavailable for the materials evaluated here. However, it is known that the tear strength of platinum-cured silicone rubbers is generally higher than that of peroxide-cured HCR due to the nature of the crosslinks (Figure 7).

As Figure 8 shows, gamma radiation reduced the tear strength of all three products. The platinum-cured HCR was most resistant to gamma radiation: A 30% decrease of tear strength occurred when it was exposed to a 75-kGy dose of radiation, whereas the tear strength of the peroxide-cured HCR exhibited a 45% reduction after receiving the same dosage.

Effect of E-Beam Irradiation: E-beam irradiation had an analogous effect to that of gamma sterilization on the mechanical properties of the silicone rubbers, albeit slightly less pronounced. The difference may be attributed to the lower degree of penetration of electrons into the silicone or to limited oxidative degradation due to the shorter exposure required for e-beam sterilization. E-beam radiation increased in the durometer hardness and tensile modulus of all rubbers tested, with a stronger effect on the properties of the peroxide-cured HCR (increase of >14 shore A and 160% in tensile modulus after an 80-kGy dosing of E-beam radiation), as Figures 9 and 10 illustrate.

As Figure 11 shows, e-beam radiation reduced the tensile elongation of all three silicone rubbers. Property degradation was more extensive for the peroxide-cured HCR, with ≤62% reduction in tensile elongation occurring after exposure to an 80-kGy dose. After the same radiation dose, 33% and 39% reductions in tensile elongation were observed for the platinum-cured LSR and HCR, respectively.

E-beam radiation slightly increased the tensile strength of LSR and platinum-cured HCR. However, it deteriorated the tensile strength of the peroxide-cured HCR by ≤39% (Figure 12). A low-level dose (10 kGy) had a minimal effect on the tear strength of all three silicone rubbers, whereas higher radiation doses led to substantial amounts of tear deterioration (Figure 13). A 35–40% reduction of tear strength was observed for all samples after exposure to an 80-kGy dose of e-beam radiation.

Effect of Ethylene Oxide Treatment: As Figures 1416 show, EtO treatment had a negligible effect on the durometer hardness, tensile modulus, and tear strength of the three silicone rubbers. A 20% higher tensile elongation was measured for LSR after EtO treatment (Figure 17). By contrast, the effects of EtO treatment on the two HCRs were negligible and within the error limit of our test.

As Figure 18 shows, the tensile strength of LSR increased by nearly a third after EtO treatment. Minor improvements in tensile strength were also observed for the two HCRs. A 13% improvement was observed for platinum-cured HCR after EtO treatment, just above the error limit of the measurement.

It is unclear why EtO treatment had such an effect on the tensile strength of LSR while the other LSR properties and those of the two HCRs remained relatively unaffected. Wacker’s proprietary filler loading content and filler surface treatment for ElastosilLR3003/50 LSR may be responsible for this observed trend.

And the Winner Is…

We investigated the effects of sterilization on three types of commercial silicone rubbers. Hardness durometer and tensile modulus in peroxide-cured HCR increased after high levels of gamma or e-beam radiation. Both radiations also reduced tear strength of silicone rubber. And they deteriorated tensile elongation and strength properties of the materials we evaluated. The extent of that deterioration is more pronounced in peroxide-cured HCR (≤45% reduction of tensile strength and 74% reduction of tensile elongation). Given these data, we do not recommend using peroxide-cured silicone rubber in any tubing or hose product that may be subjected to radiation-based sterilization procedures.

EtO treatment improved tensile strength and elongation of LSR, but it had little to no effect on the mechanical properties of the HCRs we studied. Overall, EtO sterilization had no significant negative effect on the properties of these three commercial silicone rubbers. For this reason, we consider EtO treatment to be the preferred method of sterilization for silicone rubber-based fluid transfer products.

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Authors
Emilie Gautriaud is a research engineer, Keith T. Stafford is a senior research assistant, Jennifer Adamchuk is a research information analyst, Mark W. Simon is technical director of R&D, and Duan Li Ou is a research associate, all in the fluid systems division of Saint-Gobain Performance Plastics, Northborough R&D Center, 9 Goddard Road, Northborough, ma, 01532; 1-508-351-7179, fax 1-508-351-7805; [email protected]