A combined numerical-experimental investigation of hydrodynamics of needle-free jet injection and multi-port needles



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The development of novel drug delivery systems has become increasingly important due to the need to satisfy requirements such as increased patient acceptability, enhanced occupational safety for health providers, safe disposal, and increased speed of mass vaccination in the face of pandemics or bioterror emergencies. Concerns about the fear of needles (trypanophobia), needle reuse, and needle-stick injuries necessitate the use of needle-free drug delivery methods. A jet injection is a needle-free drug delivery method, where a liquid drug is propelled at high pressures through a narrow orifice (~ 150 microns) to generate a high-speed liquid jet (~ 150 m/s) sufficient to puncture tissue and deposit liquid inside the tissue. Transdermal drug delivery using spring-powered jet injection has been studied for several decades and continues to be highly sought after due to the advent of targeted needle-free techniques, especially for non-Newtonian fluids such as DNA vaccines. In the present thesis, we mainly focus on the study of spring-powered needle-free jet injectors (NFJIs). For NFJIs, using a combined experimental – numerical (CFD simulations) approach, we examine the effect of cartridge geometry and fluid rheology on characteristics such as jet speed, pressure losses, and shear layer growth. We characterize the hydrodynamic performance of cartridge geometries using empirical correlations of Euler number (Eu) versus Reynolds number (Re) and propose a novel methodology to design asymmetric sigmoid-taper cartridge geometries using Richard’s function. We further observe that fluid viscosity and cartridge-plunger friction are the two most important considerations in tailoring the cartridge geometry to achieve a given jet velocity. Using cartridge geometry-specific Eu–Re correlations to estimate pressure losses, we extend the applicability of an existing mathematical approach to accurately predict jet hydrodynamics. By studying a range of cartridge geometries, we see that the power of actuation sources and nozzle geometry can be tailored to deliver drugs with different fluid viscosities to the target tissue region. Additionally, we report on an experimental study of high-speed liquid jets ejected into partial vacuum environments, which has applications for the use of negative pressure modules in jet injector systems to stabilize the skin position and tension during injections. We report that use of negative pressures is viable for jet injector applications and postulate an optimal range of working pressures and configurations. Further, we demonstrate the feasibility of multi-orifice jet injections, which can be used for the simultaneous delivery of multiple jets at distinct tissue penetration depths. Combined drug delivery into intramuscular and intradermal tissue has been shown to elicit a multi-faceted, enhanced immune response. Here, we consider a wide orifice (200 microns – 400 microns) for intramuscular drug delivery and a narrow orifice (100 microns) for intradermal drug delivery. Here, we identify the key parameter affecting the jet velocities through the orifices to be the ratio of orifice length to orifice diameter, especially for the laminar flow regime. Lastly, for a needle-based drug delivery, we report a novel adaptation of a conventional hypodermic needle, which is shown to result in superior fluid dispersion in tissue. This is achieved using multiple outlets (ports) along the needle length. Here, we study the effect of port shape and size on the hydrodynamics and the fluid dispersion in muscle tissue. The proposed design of the multi-port needle geometry is potentially cost-effective for mass production and may prove to be an attractive alternative for conventional hypodermic needles, especially for electroporation-assisted drug delivery. As a result of the mechanistic studies presented here, we provide useful hydrodynamic insight and guidelines to design and manufacture needle-free jet injectors and multi-port needles.

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Drug Delivery Devices, Fluid Dynamics, Needle-Free Jet Injection, Multi-Port Needles, Multi-Orifice Injectors, CFD, DNA Vaccines, Medical Devices, Rheometry, Electroporation, Enhanced Immunity