Acceptability of the multi-jet injection technique

Each participant will receive two 'multi-jet injection' interventions and one control intervention. To assess the effects of injection volume and viscosity we will perform multi-jet injections at two different volumes, 2 mL and 5 mL, and do so with fluids of three different viscosities: 1 mPa.s, 30 mPa.s, and 100 mPa.s. All interventions on each participant will be performed with the same fluid; thus, participants will be randomly divided into three groups to test the three different viscosities. Isotonic saline will be used for the 1 mPa.s fluid while viscous placebo solutions will be prepared at viscosities of 30 mPa.s and 100 mPa.s. Multi-jet injection involves the delivery of a fluid as multiple simultaneous high speed jets. The jets are small (0.2 mm or less) and travelling fast enough (>120 m/s) that they can break through the skin layers and deliver themselves to the subcutaneous or intramuscular tissue. In this study participants will receive two multi-jet injection, one of 2 mL and the other of 5 mL, in the abdomen region performed by a nurse that has been trained to use a multi-jet injector. The injections will each take <1 s. Pain will be measured using a 100 mm visual analogue scale ~30 s after and 1 day after the injections. Participants will also be asked which of the interventions they preferred after both are completed (at least 5 mins after the final injection) and again 1 day after the injections. A nurse will also record the existence of any injection site reactions (redness, swelling, bleeding, or bruising) immediately after and 1 day after the injections. The investigators will also note any evidence of the fluid remaining on the skin surface, or otherwise failing to inject. Injections will be administered into the subcutaneous tissue of the anterior abdominal wall. The abdomen will be divided into four quadrants (with the navel at the centre of the 4 regions) with one intervention performed in each quadrant and one quadrant left without intervention. The location and order of interventions will be randomised. Participants will be aware of which interventions they are receiving and scoring (i.e. they will not be blinded). The interventions will take place at a clinical trial facility within the University of Auckland (Grafton, Auckland, NZ). A 1 hour visit will be required to conduct the interventions then the participants will be asked to complete a questionnaire (via email) 24hrs after the interventions. We will prepare viscous placebo solutions using polyethylene glycol (PEG-400) to increase the viscosity of injectable isotonic saline solution. PEG-400 is widely approved (including FDA) for use in injectable formulations, typically as an excipient, due to its biocompatibility and non-immunogenic properties. Prior to the clinical trial we will perform testing to understand precisely what concentrations of PEG-400 are needed to achieve 30 mPa.s and 100 mPa.s viscosities. We will also confirm that the pH and osmolarity of the solutions do not significantly deviate from the physiological range at these concentrations as these factors could cause increased injection pain. We anticipate that PEG-400 will produce safe solutions of viscosities 30 mPa.s and 100 mPa.s at concentrations much lower than are used in other approved injectable formulations. We will source injectable-grade PEG-400 from CD-Bioparticles (or similar). To ensure sterility we will either mix sterilised products to the desired concentration in the clinic immediately before participant arrival or will premix and resterilise the solution via autoclave.