Download Design and Development of a Dual

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: [email protected]
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.
METHODS
Outer plunger
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 (CyclicOlefin-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).
Inner plunger - Rear
Syringe body
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)
Inner plunger - Front
THANKS
Figure 1. A: Plunger ready for freeze drying, B: Sealed, C: Syringe ready for use, D: After
injection
To Lasse Johanson for producing the prototypes and to Ditte R. Poulsen
for her enthusiasm and diligence during her Master’s project work.
Figure 3.
Filled plunger