Effect of Processing Parameters on the Physical Stability of Silicone Coatings

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Prefilled syringes have emerged as a container of choice for the storage and delivery of protein pharmaceuticals. This is due to a number of factors including greater medication safety resulting from reduced dosage errors, ease of use, and significantly reduced overfill requirements (1,2). Proper functionality of the prefilled syringes is achieved by lubricating the syringe barrel and plunger tip. For the past several decades, silicone oil has been the material of choice for this purpose. Recently, silicone oil has been implicated in causing enhanced protein aggregation in formulations delivered through prefilled syringes (3–5). The process of protein aggregation in formulations stored in prefilled syringes can, in general, be ascribed to the following steps: protein adsorption to the hydrophobic silicone oil/water interface, surface-induced protein denaturation, desorption of the denatured species, and aggregate formation following association with similar molecules in the bulk. Since protein binding to the silicone oil constitutes the earliest step in this aggregation process, it is critical to inhibit/reduce this binding. In prefilled syringes, silicone oil is available in two forms with which a protein can interact: surface bound and free. Surface-bound silicone oil provides a static interface with water in a device. Free silicone oil is present because of the application of excess silicone oil or a poor coating process, which may leach into the bulk. The leached silicone oil poses an additional concern as it provides an increased interfacial area for protein adsorption. Moreover, from a regulatory perspective, the enhanced particulate load because of silicone oil leaching can be a problem (6). Since the only purpose of silicone oil in prefilled syringes is to provide lubricity for a smooth plunger movement, it is important to optimize the amount of silicone oil that is applied to the surface to maintain an optimum syringe gliding force without generating any excess silicone oil on the surface. Excluding this excess silicone oil, which is prone to leaching, will result in a reduction in the silicone oil/water interfacial area with which a protein can interact, making the protein binding to the silicone oil a rate-limiting step in the process of silicone oil-induced protein aggregation. As more and more biologics are becoming available in prefilled syringes, it is critical to reassess the process of silicone oil coating in syringes. In a recent study, silicone migration from cyclic olefin copolymer syringes, coated with silicone, was studied as a function of curing process and formulation parameters (7); however, most of the work done by the industries in this area is proprietary and is seldom published. From a point of gaining a mechanistic understanding about the effect of different parameters on the stability of silicone coating at a surface against leaching, we evaluated the physical stability of silicone films in distilled water as a function of curing temperature, the applied amount, and viscosity of silicone fluid.