Hydrodynamics of a dual-orifice needle-free jet injector

Abstract

In the recent literature, it has been shown that an enhanced, multi-faceted, balanced immune response can be generated using a combined intradermal (ID) and intramuscular (IM) delivery of vaccines, especially for novel DNA vaccines. However, needle-based injection for a combined ID/IM delivery may require separate injections, which may prove to be time consuming, and impractical for mass immunizations. In contrast, a novel multi-orifice jet injector could be used to deliver drugs at multiple penetration depths simultaneously, which may provide advantages such as ease of operation, elimination of sharps, and short injection timeframe (O (10 m)).Here, we consider a dual-orifice geometry with both a wide orifice (200 μm–400 μm) for IM drug delivery and a narrow orifice (100 μm) for ID drug delivery. Using numerical simulations, we found that, at a fixed upstream pressure, jet velocities through wide and narrow orifices do not vary significantly for low-viscosity fluids (≲4%). However, it was previously hypothesized that the jet power, Pj=π8ρdj2vj3, is a more appropriate parameter to characterize tissue penetration depth. Thus, the jet power could vary by a factor of ∼10, yielding different depths for the two orifices. Using non-dimensional analysis via Euler (Eu) and Reynolds (Re) numbers, we characterize the role of orifice geometry and driving pressure, to generate geometry-specific correlations in the Eu–Re parameter space to estimate the jet velocity and pressure losses. We also elucidate the orifice size ratios that are best suited for fractional doses of ∼100 μL to intradermal tissue from a total injection of 1 ml.Preliminary experiments to visualize the penetration of wide and narrow jet streams into gelatin and pork substrates showed that the wide jet stream leads to substantially greater penetration depth than the narrow jet stream. In summary, we provide the initial feasibility of simultaneous delivery of a drug to multiple penetration depths from the same injection cartridge using the needle-free jet injection technique.