PURPOSE

1. UNIVERSITY OF COPENHAGEN Poster # W4001 Design and Development of a Dual-Chamber Syringe Daniel Bar-Shalom School of Pharmaceutical Sciences, University of Copenhagen. Universitetsparken 2, 2100 Copenhagen Ø, Denmark and Bioneer A/S, Kogle Alle 2, 2970 Hørsholm, Denmark. Email: daniel.barshalom@sund.ku.dk MEDILET Outer plunger Inner plunger - Front PURPOSE RESULTS – Usage and Stability Dual-Chamber prefilled syringes enable the production of injectables where the mixing of components must take place at the last moment because of stability issues or functionality. The existing products are somewhat complex, mainly due to the presence of air in both chambers, and not appropriate for emergency situations. A different approach is proposed. The first iterations of the PIP demonstrated that it is possible to effect a satisfactory mixing of the components in the absence of air but modifications were needed to ensure the total ejection of the mixed contents (elimination of the dead-volume) and to devise a way to directly lyophilize drugs into the compartment by using conventional equipment. The COC vs. glass studies revealed that, for the protein studied, COC can substitute glass in this design except for the formulations where the antioxidant was ascorbate. Syringebody Inner plunger - Rear METHODS The starting point was a Plunger-In-Plunger (PIP) approach. The design consists of: A conventional syringe body, a first – hollow - plunger movably inside the syringe body and a second plunger movably inside the cavity of the first plunger. The second plunger consists of two parts which, when coupled, define a sealed compartment where one of the components resides (usually the drug). The second component, usually a liquid diluent, is contained inside the syringe body, in front of the plunger. When the second plunger is pressed, the sealed compartment opens and the components mix aided by a structure mounted at the tip of the second plunger and then the composition is ready to be injected. The development was conducted in silico and by building physical prototypes. The PIP can be produced in glass or in plastic (Cyclic-Olefin-Copolymer, COC). Studies were performed to evaluate stability of a protein sensitive to humidity and oxidation in containers of both materials, using three different antioxidant systems and measuring protein conformational and chemical stability (data on file). Figure 2. The parts of the syringe. The Body used was a standard BD 10ml CONCLUSIONS • A new dual-Chamber Syringe was developed. The design proves to be simple to produce and amenable to small scale, semi-automatic production as well as to large scale production. The lyophilization can be carried out in unmodified freeze-drying equipment. RESULTS - Lyophilization The inner plungers were successfully filled, the “rear inner plungers” inserted (as in FIGURE 1 – A) and lyophilized in a conventional unmodified Christ Epsilon 2-4 LSC (a perforated aluminium block was used to prevent the plungers from tilting). While under vacuum, the lyophilizate was sealed by lowering the upper plate of the dryer until the rear and front inner plungers were coupled ((as in FIGURE 1 – A) THANKS Figure 3. Filled plunger • To Lasse Johanson for producing the prototypes and to Ditte R. Poulsen for her enthusiasm and diligence during her Master’s project work. Figure 1. A: Plunger ready for freeze drying, B: Sealed, C: Syringe ready for use, D: After injection