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.