Characterization of needle-assisted jet injections

Hypodermic injections have been the standard for transcutaneous drug delivery for many years. However, needle phobia, pain, and risks of needle-stick injuries have manifested in poor patient compliance. Needle-free jet injections (NFJI) have been developed to address these drawbacks but the reliability of dose and depth of delivery have been limited by a lack of control over jet parameters, and by variability in the skin's mechanical properties among individuals. Moreover, the device size and cost have been restrained by the high pressure (>= 20 MPa) required to penetrate the skin. Needle-assisted jet injections have been proposed to improve delivery reliability of conventional jet injectors by penetrating the skin with a short needle (<5 mm) and thereby allowing jet delivery to a desired injection depth at a reduced pressure. This study characterized needle-assisted jet injections performed after first penetrating the skin with a 1.5 mm needle, examining the effect of needle size on jet parameters, and evaluating injection performance in porcine skin. A voice-coil actuated jet injector was modified to incorporate needles of 30 G, 31 G and 32 G. A series of pulse tests was performed to compare jet velocity and injection volume across the needle sizes, where it was found that the jet velocity and injection volume achieved with 32 G needles were 13% and 16% lower, respectively, than with 30 G. In contrast, there was no significant difference in jet velocity and injection volume between 30 G and 31 G needles, suggesting that a reduction of 10 mu m in the mean inner diameter of the 31 G needle has minimal impact on jet velocity and injection volume. Injection studies performed in porcine skin revealed that injections driven by fluid pressures ranging between 0.8 MPa and 1.4 MPa were able to achieve substantial injectate penetration (similar to 10 mm) and delivery (similar to 100 mu L) into subcutaneous fat regardless of needle size, in a period of 40 ms. The required pressures are an order of magnitude lower than those used in NFJI, yet still maintain the high-speed nature of jet injection by achieving a delivery rate of 2.25 mL/s. The lower pressures required in needle-assisted drug delivery can lead to reduced device size and cost, as well as reduced shear stresses during jet injection and can therefore minimise the potentially adverse effect of shear on the structural integrity of proteins, vaccines and DNA. (C) 2016 Elsevier B.V. All rights reserved.