Sharmy Blows, Robert Hill, John Wilmot, Beth Belluscio, Kevin Cleary, David Lindisch, Robin Tucker, Emmanuel Wilson, Rajesh Shukla

Parenteral routes of drug administration are often selected to optimize actual dose of drug delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well as maximize the speed of onset. Intramuscular (IM) delivery can be preferred to intravenous delivery when initiating intravenous access is difficult or impossible. Drugs can be injected intramuscularly using a syringe or an automated delivery device (autoinjector). Investigation into the IM delivery dynamics of these methods may guide further improvements in the performance of injection technologies. Two porcine model studies were conducted to compare differences in dispersion of injectate volume for different methods of IM drug administration. The first study compared the differences in the degree of dispersion and uptake of injectate following the use of a manual syringe and an autoinjector. The second study compared the spatial spread of the injected formulation, or dispersion volume, and uptake of injectate following the use of five different autoinjectors (EpiPen(®) [0.3 mL], EpiPen(®) Jr [0.3 mL], Twinject(®) [0.15 mL, 0.3 mL], and Anapen(®) 300 [0.3 mL]) with varying needle length, needle gauge, and force applied to the plunger. In the first study, the autoinjector provided higher peak volumes of injectate, indicating a greater degree of dispersion, compared with manual syringe delivery. In the second study, EpiPen autoinjectors resulted in larger dispersion volumes and higher initial dispersion ratios, which decreased rapidly over time, suggesting a greater rate of uptake of injectate than the other autoinjectors. The differences in dispersion and uptake of injectate are likely the result of different functional characteristics of the delivery systems. Both studies demonstrate that the functional characteristics of the method for delivering IM injections impact the dispersion and uptake of the material injected, which could significantly affect the pharmacokinetics and, ultimately, the effectiveness of the drug.