The effect of jet speed on large volume jet injection.

Jet injection presents a promising alternative to needle and syringe injection for transdermal drug delivery. The controllability of recently-developed jet injection devices now allows jet speed to be modulated during delivery, and has enabled efficient and accurate delivery of volumes up to 0.3 mL. However, recent attempts to inject larger volumes of up to 1 mL using the same methods have highlighted the different requirements for successful delivery at these larger volumes. This study aims to establish the jet speed requirements for delivery of 1 mL of liquid using a controllable, voice coil driven injection device. Additionally, the effectiveness of a two-phase jet speed profile is explored (where jet speed is deliberately decreased toward the end of the injection) and compared to the constant jet speed case. A controllable jet injection device was developed to deliver volumes of 1 mL of liquid at jet speeds >140 m/s. This device was used to deliver a series of injections into post-mortem porcine tissue in single and two-phase jet speed profiles. Single-phase injections were performed over the range 80 m/s to 140 m/s. Consistent delivery success (>80% of the liquid delivered) was observed at a jet speed of 130 m/s or greater. Consistent penetration into the muscle layer coincided with delivery success. Two-phase injections of 1 mL were performed with a first phase volume of 0.15 mL, delivered at 140 m/s, while the injection of the remainder of fluid was delivered at a second phase speed that was varied over the range 60 m/s to 120 m/s. Ten two-phase injections were performed with a second phase speed of 100 m/s producing a mean delivery volume of 0.8 mL ± 0.2 mL, while the single-phase injections at 100 m/s achieved a mean delivery volume of 0.4 mL ± 0.3 mL. These results demonstrate that a reduced jet speed can be used in the later stages of a 1 mL injection to achieve delivery success at a reduced energy cost. We found that a jet speed approaching 100 m/s was required following initial penetration to successfully deliver 1 mL, whereas speeds as low as 50 m/s have been used for volumes of <0.3 mL. These findings provide valuable insight into the effect of injection volume and speed on delivery success; this information is particularly useful for devices that have the ability to vary jet speed during drug delivery.