Tissue Resistance during Large-Volume Injections in Subcutaneous Tissue of Minipigs.

Abstract

Injection devices for administration of biopharmaceuticals enable subcutaneous self-administration by patients. To meet patient specific capabilities, injection forces need to be characterized. We address the open question of whether tissue resistance significantly contributes to overall injection forces, especially for large injection volumes. Subcutaneous tissue resistance was systematically quantified for injection volumes up to 11mL depending on viscosity (1-20mPa·s) and injection rates (0.025-0.2mL/s) using Göttingen Minipigs as the animal model. The contribution of an artificially applied external force at the injection site simulating autoinjector needle cover depression was tested between 2.5-7.5N. Tissue resistance reached average values of ~120mbar for injection volumes up to 11mL independent of viscosity and injection rate, and maximum values of 300mbar were determined. Artificially applied external forces led to higher values, independent of the absolute applied force - maximum values of 1bar were obtained when injecting 4.5mL of the 20mPa·s solution at an injection rate of 0.1mL/s with the application of an artificial 5N force, corresponding to ~450mbar. All conditions yield defined injection sites suggesting tissue resistance is defined by mechanical properties of the subcutaneous tissue. We set our results in relation to overall injection forces, concluding that maximum values in tissue resistance may cause challenges during subcutaneous injection when using injection devices. Graphical abstract.