In the medical device industry, silicone oil is a ubiquitous lubricant used in the manufacture and assembly of medical components, and also as the terminal lubricant for proper device operation. In prefilled syringes, problems arise when micro-droplets of silicone oil migrate into the drug medium and act as a contaminant which can potentially react with the packaged drug. In the case of biological drugs, silicone oil contamination has been implicated in protein conformational changes and aggregation where even a small fraction of aggregated proteins can reduce biological activity and/or result in undesired immunogenicity. These particles and conformational changes are especially troubling in ophthalmic applications where the use of intravitreal injections for the treatment of retinal disorders has become a common procedure. Silicone oil droplets have been reported to remain in the eye long after the intravitreal injection, causing several patient related complications such as ?visual floaters?. Syringes for prefilled applications predominantly use silicone oil as a lubricant because of its inert and lubricious properties, along with its long-term stability data and well known toxicology profile. However, silicone oil droplets in drug formulations pose a significant problem for many drugs where the prefilled format is preferred. Therefore, an advanced silicone lubrication technology for prefilled devices is highly desired. TriboFilm Research, Inc. proposes the development of our advanced silicone lubrication system, TriboLink-Si?, for use in prefilled syringes. The TriboLink-Si? technology is based on crosslinking the medical grade silicone oil lubricant using an inert, atmospheric gas plasma technology to create a lubricating coating that is resistant to migration and leads to less lubricant extraction into the drug product. In Phase I, TriboFilm Research optimized the TriboLink-Si? coating system to provide syringes with similar force profiles and dramatically reduced particle loads compared to standard siliconized syringes. In collaboration with Professor LaToya Jones Braun, TriboLink-Si? was analyzed in a variety of commonly used excipients and model protein formulations to establish the feasibility of using this advanced coating in parenteral containers. The TriboLink-Si? lubricant proved to be comparable to silicone oil in terms of plunger force performance and the stability of model proteins, while reducing the particulate contamination by up to two orders of magnitude and meeting the USP <789> requirements for particulates in ophthalmic containers. Phase II will build on the Phase I findings to prove the commercial viability of the TriboLink-Si? technology from a manufacturing standpoint. The TriboLink-Si? coating parameters will be optimized using scalable processing equipment to achieve extremely low particulate levels and acceptable plunger forces. The compatibility of the TriboLink-Si? coating with respect to general formulation parameters, protein stability, and aggregation will be examined using a pharmaceutically relevant therapeutic protein to build further customer confidence and market adoption. Additionally, an extraction study will be performed on TriboLink-Si? coated syringes to evaluate the toxicological safety of the coating while generating data for use in regulatory filings. This project will culminate with the production of a pilot coating machine to demonstrate how all TriboLink-Si? coating parameters can be integrated into a continuous manufacturing process. The pilot machine will document the know-how for full-scale manufacturing that can be transferred to potential licensees, while also producing TriboLink-Si? coated syringes that can be provided to customers for evaluation. The medical device and pharmaceutical industries have long desired an advanced silicone lubrication technology for prefilled syringes that does not affect the stability of the packaged drug in solution. If successful, TriboLink-Si? will provide the advanced lubrication needed to package sensitive biopharmaceuticals in prefilled syringes.

Public Health Relevance

Ease of use, reduction in drug wastage, minimization of medical dosing errors, along with many other enticing factors provide compelling reasons for packaging drugs in single-dose prefilled syringe formats. Silicone oil, which serves as a lubricant for easy operation of the syringe, can contaminate the drug product and adversely interact with sensitive pharmaceutical products. Contamination of drug products with lubricant particles is especially detrimental in ophthalmic drugs where the use of intravitreal injections of monoclonal antibodies for the treatment of retinal disorders has become a common procedure. Patient complaints, such as sustained increases in intraocular pressure and silicone oil ?floaters? in the field of vision, are prevalent after intraocular injection of anti-VEGF compounds for the treatment of macular degeneration. The proposed TriboLink-Si? coating system provides an advanced lubrication alternative that overcomes the problems of lubricant migration and drug contamination in intravitreal injections and a broad range of other parenteral applications.

National Institute of Health (NIH)
National Eye Institute (NEI)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1)
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Wujek, Jerome R
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Tribofilm Research, Inc.
United States
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