Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

Abstract

AimThe primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance.MethodsThe study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8–10, and 15–20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images.ResultsViscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers.ConclusionThe results of this study suggest that solutions of up to 3 mL and up to 15–20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain.

An optimised protocol for platelet-rich plasma preparation to improve its angiogenic and regenerative properties

“…These data suggest that apart from increasing angiogenesis, cold pre-incubation may also be beneficial for delaying PRP coagulation inside the syringe in protocols in which PRP is administered through injection immediately after the addition of calcium (e.g. intraarticular, intraosseous, or subcutaneous) 29 , thereby reducing pain associated with the injection of viscous solutions 30 , 31 . On the other hand, several controversies are associated with storage of platelets at 4 °C, since it may induce platelet activation as well as their rapid clearance from circulation 32 .…”

Classification and mitigation of negative injection experiences with biologic medications

“…In contrast, a study by Heise et al () reported that injection speed had no effect on pain, but injection pain increased with volumes of ≥1.2 mL. Finally, Schwarzenbach et al () found that rate and volume had no effect on injection pain while viscosity had a significant effect, with high viscosity being less painful than medium or low viscosity. The mechanism behind this finding deserves further exploration.…”

Modeling and mitigation of high-concentration antibody viscosity through structure-based computer-aided protein design

“…For a successful SC administration of an antibody therapeutic with optimal syringeability and minimal pain, the preferred viscosity of the material is lower than 20 centipoise (cP) at the desired concentration. [7] In addition, concentrations higher than the projected dose are often required during the manufacturing process to enable buffer exchange and formulation, and excess viscosity can lead to clogged filters and loss of material. [6] Strategies for mitigation of high-concentration viscosity include optimization of the formulations, optimization of the sequence or screening of candidate molecules for optimal properties.…”