Research Project
8832423
DESCRIPTION (provided by applicant): 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 undesirable 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 complications. 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 a prefilled format is preferred. Therefore, an advanced silicone lubrication technology for prefilled devices is highly desired. TriboFilm Research, Inc. proposes the development of their advanced silicone lubrication system, TriboLink, for use in prefilled syringes. The TriboLink technology is based on crosslinking a silicone oil lubricant using an inert gas plasma technology to create a lubricating coating that is resistant to migration and leads to less lubricant extractin into the drug product. In Phase I, TriboFilm Research will optimize the TriboLink coating and provide syringes with similar force profiles and dramatically reduced particle loads compared to standard siliconized syringes. In collaboration with Professor LaToya Jones Braun, TriboLink will be 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 lubrication process will be optimized using a design of experiments to produce coatings with low syringe extrusion forces and low particle counts. Particles will be measured using light obscuration and microflow imaging to determine the number of particles present and distinguish between different types of particles. With an optimized coating process, longer term stability data will be accumulated to establish the superiority of the TriboLink lubrication process compared to standard silicone oil. Activity assays with a model protein will give insight into the effects that the reduced particulate burden, observed in TriboLink syringes, has on the efficacy of a protein molecule. In Phase II, therapeutic protein stability will be examined using fluorescence spectroscopy, mass spectrometry, and microflow imaging. Toxicity and function of therapeutic proteins stored in TriboLink lubricated syringes will also be examined using in vitro (cell-based) and in vivo (rodent) models. 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 will provide te advanced lubrication needed to package sensitive biopharmaceuticals in prefilled syringes.
