Jet injection technology has become the alternative drug delivery method of conventional needle-based injection due to its obvious advantages. In order to meet the demand for larger volume injection, the pneumatic jet injection systems have efficiently administrated vaccine up to 1 mL in human. Our recent study has also demonstrated that controlling the driving pressure enabled the pneumatic jet injection system to deliver larger volumes of drugs to target sites at desired rates and times. This work continues to explore the optimal two-phase driving pressure combination with better injection efficiency for typical larger-volume (1.0 mL) jet injection with controllable pneumatic jet injection system. Under the combination of a first phase driving pressure of 1.00 MPa and a second phase driving pressure ranging from 0.25 to 0.90 MPa, dynamic characteristics, dispersion characteristics and pharmacokinetic characteristics of this controllable jet injection system were quantitatively analyzed. In all experiments, it was confirmed that the optimal driving pressure combination of 1.0 mL ejection volume was close to (1.00-0.50) MPa. That is, the injection velocities of 151.85 m/s and 102.01 m/s for the first and second phase respectively facilitated better injection performance with a controlled release of 1.0 mL ejection volume. This strategy is practical for facilitating the clinical application of large-volume controllable jet injection systems.

Needle-free injection (NFI) technology is a promising alternative to conventional syringe injection, as it mitigates needle-related complications and enhances patient compliance. However, achieving the controlled and efficient dispersion of larger-volume formulations (>1 mL) within tissues remains a significant challenge. This study presents a novel pneumatic NFI system that uses a two-phase driving mode to regulate driving pressure and duration with an ejection volume of 1.0–2.0 mL. The integrated pressure stabilization unit significantly reduces pressure fluctuations during the initial injection phase, generating a more stable and uniform spray distribution. It is designed to produce an ideal elliptical dispersion effect while eliminating splatter, enabling controlled large-volume delivery. Jet impact experiments were conducted to investigate the dynamic characteristics of microjets generated by conventional single-phase and novel two-phase driving modes. Furthermore, the influence of the driving mode on the dispersion behaviors of microjets in agarose gels was explored through high-speed imaging of gel injections. The results demonstrate that the two-phase driving mode produces a distinct two-phase jet pressure profile. Compared to the single-phase mode, the two-phase mode produced a significantly larger dispersion width at equivalent initial driving pressures. This promotes more uniform lateral drug distribution and achieves a higher percentage of liquid drug delivery in gels. Furthermore, favorable driving pressure combinations were identified for different volumes: (1.25–0.25) MPa for 1.0 mL, (1.25–0.50) MPa for 1.5 mL, and (1.50–0.50) MPa for 2.0 mL. This provides a practical basis for optimizing clinical parameters and advancing the development of controllable NFI systems.