(208f) Evaluating the Syringeability of Drug Products Using Mechanistic in-Silico Modeling

The syringeability of drug products refers to determining that the extrusion forces necessary to push the drug product out of the syringe are within acceptable limits. The drug properties as well as means of its delivery are subjected to change during their development cycles and requires repeating characterization testing that takes weeks to complete. Therefore, a mechanistic in-silico model has been developed to compute the extrusion force required for dosing saving tremendous amount of time and cost as a result. The extrusion force is required to overcome two resistive components: friction resistance from the lubricant and drug product resistance from the fill. The friction force depends on the area of contact between the stopper and the syringe, the viscosity of the lubricant, and the film thickness. Finite element contact simulation was used to obtain the area of contact between the stopper and syringe at different pressure levels on the stopper face. Similarly, finite element flow simulation was used to compute the drug pressure on the stopper face. The addition of these two components results in the total extrusion force. This model takes drug properties (density and viscosity), fill volume, syringe and needle geometry, stopper shape and materials, and injection time as inputs. This model can perform large scale DOE (Design of Experiment) type studies by sweeping input parameters across their tolerance band and/or acceptable ranges. This work describes such a high-fidelity in silico model, and present the results of these simulations, including experimental validation. The benefits are arriving at a greater fundamental understanding, which translates into design decisions with greater speed and confidence by product teams.