Improved Silicone Lubrication to Reduce Sub-Visible Particles in Parenteral Containers.

PROJECT SUMMARYIn the medical device industrysilicone oil is a ubiquitous lubricant used in the manufacture and assembly of medical componentsand also as the terminal lubricant for proper device operationIn prefilled syringesproblems arise when micro droplets of silicone oil migrate into the drug medium and act as a contaminant which can potentially react with the packaged drugIn the case of biological drugssilicone 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 immunogenicityThese 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 procedureSilicone oil droplets have been reported to remain in the eye long after the intravitreal injectioncausing several patient related complications such asvisual floatersSyringes for prefilled applications predominantly use silicone oil as a lubricant because of its inert and lubricious propertiesalong with its long term stability data and well known toxicology profileHoweversilicone oil droplets in drug formulations pose a significant problem for many drugs where the prefilled format is preferredThereforean advanced silicone lubrication technology for prefilled devices is highly desiredTriboFilm ResearchIncproposes the development of our advanced silicone lubrication systemTriboLink Sifor use in prefilled syringesThe TriboLink Sitechnology is based on crosslinking the medical grade silicone oil lubricant using an inertatmospheric gas plasma technology to create a lubricating coating that is resistant to migration and leads to less lubricant extraction into the drug productIn Phase ITriboFilm Research optimized the TriboLink Sicoating system to provide syringes with similar force profiles and dramatically reduced particle loads compared to standard siliconized syringesIn collaboration with Professor LaToya Jones BraunTriboLink Siwas analyzed in a variety of commonly used excipients and model protein formulations to establish the feasibility of using this advanced coating in parenteral containersThe TriboLink Silubricant proved to be comparable to silicone oil in terms of plunger force performance and the stability of model proteinswhile reducing the particulate contamination by up to two orders of magnitude and meeting the USP andltandgtrequirements for particulates in ophthalmic containersPhase II will build on the Phase I findings to prove the commercial viability of the TriboLink Sitechnology from a manufacturing standpointThe TriboLink Sicoating parameters will be optimized using scalable processing equipment to achieve extremely low particulate levels and acceptable plunger forcesThe compatibility of the TriboLink Sicoating with respect to general formulation parametersprotein stabilityand aggregation will be examined using a pharmaceutically relevant therapeutic protein to build further customer confidence and market adoptionAdditionallyan extraction study will be performed on TriboLink Sicoated syringes to evaluate the toxicological safety of the coating while generating data for use in regulatory filingsThis project will culminate with the production of a pilot coating machine to demonstrate how all TriboLink Sicoating parameters can be integrated into a continuous manufacturing processThe pilot machine will document the know how for full scale manufacturing that can be transferred to potential licenseeswhile also producing TriboLink Sicoated syringes that can be provided to customers for evaluationThe 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 solutionIf successfulTriboLink Siwill provide the advanced lubrication needed to package sensitive biopharmaceuticals in prefilled syringes PROJECT NARRATIVEEase of usereduction in drug wastageminimization of medical dosing errorsalong with many other enticing factors provide compelling reasons for packaging drugs in single dose prefilled syringe formatsSilicone oilwhich serves as a lubricant for easy operation of the syringecan contaminate the drug product and adversely interact with sensitive pharmaceutical productsContamination 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 procedurePatient complaintssuch as sustained increases in intraocular pressure and silicone oilfloatersin the field of visionare prevalent after intraocular injection of anti VEGF compounds for the treatment of macular degenerationThe proposed TriboLink Sicoating 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