Understanding Subcutaneous Tissue Pressure for Engineering Injection Devices for Large-Volume Protein Delivery.
Subcutaneous injection allows for self-administration of monoclonal antibodies using prefilled syringes, autoinjectors, and on-body injector devices. However, subcutaneous injections are typically limited to 1 mL due to concerns of injection pain from volume, viscosity, and formulation characteristics. Back pressure can serve as an indicator for changes in subcutaneous mechanical properties leading to pain during injection. The purpose of this study was to investigate subcutaneous pressures and injection site reactions as a function of injection volume and flow rate. A pressure sensor in the fluid path recorded subcutaneous pressures in the abdomen of Yorkshire swine. The subcutaneous tissue accommodates large-volume injections and with little back pressure as long as low flow rates are used. A 1 mL injection in 10 seconds (360 mL/h flow rate) generated a pressure of 24.0 ± 3.4 kPa, whereas 10 mL delivered in 10 minutes (60 mL/h flow rate) generated a pressure of 7.4 ± 7.8 kPa. After the injection, the pressure decays to 0 over several seconds. The subcutaneous pressures and mechanical strain increased with increasing flow rate but not increasing dose volume. These data are useful for the design of injection devices to mitigate back pressure and pain during subcutaneous large-volume injection.
Drug Delivery and Device Development, Biopharmaceutical Development, MedImmune LLC., Gaithersburg, Maryland 20878. Electronic address: doughtyd@medimmune.com.
Diane V
DV
Doughty
Drug Delivery and Device Development, Biopharmaceutical Development, MedImmune LLC., Gaithersburg, Maryland 20878.
Corbin Z
CZ
Clawson
Drug Delivery and Device Development, Biopharmaceutical Development, MedImmune LLC., Gaithersburg, Maryland 20878.
William
W
Lambert
Drug Delivery and Device Development, Biopharmaceutical Development, MedImmune LLC., Gaithersburg, Maryland 20878.
J Anand
JA
Subramony
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004487:Edema / Q000209:etiology; D004867:Equipment Design; D004890:Erythema / Q000209:etiology; D007279:Injections, Subcutaneous / Q000009:adverse effects; D010146:Pain; D011312:Pressure; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D040521:Subcutaneous Tissue / Q000502:physiology*; D013552:Swine; D013594:Syringes
D000911:Antibodies, Monoclonal; D011506:Proteins
biocompatibility; device; injectables; injectors; monoclonal antibody; pain; parenteral; physiological model; skin; subcutaneous