Does needle clogging change the spatial distribution of injected drug in tissue? New insights by X-ray computed tomography.

Abstract

Prefilled syringes (PFS) are primary packaging materials that offer convenience and safety for subcutaneous injection of parenteral drug solutions. However, an increasingly common problem with the trend towards higher drug concentrations is the clogging of the needle during storage due to evaporative water loss and consequent solidification of the drug. In contrast to all previous studies on this topic, this work focuses on pharmacokinetically relevant aspects and investigates the effects of needle clogging on the spatial distribution of the injected drug in the tissue. X-ray computed tomography (XCT) (both tube-based and synchrotron-based) was used to visualize and analyze the spreading pattern and the fate of the injected liquid in porcine skin. By using controlled injection and force measurement the tissue distribution was correlated with the plunger force profile and the fluid dynamics of the jet. Studies of monoclonal antibody solution demonstrate that clogs, which are formed by evaporation of water and solidification of drug solution in the needle tip, usually dissolve in the flow of the liquid during injection. In the initial injection phase, the liquid jet starts to escape the needle only through a narrow channel in the clog. The resulting high dynamic pressure can alter the distribution of the liquid in the tissue, causing a long tail of liquid that penetrates deep into the fibrous network of the subcutaneous layer. However, the volume of this tail was calculated to be low relative to the overall volume of the injected drug solution (less than 2.4%) and is therefore unlikely to have a significant effect on the absorption kinetics of the injected drug. In addition, it was shown that if a clog were to enter the tissue, it would quickly dissolve.