Transdermal drug delivery by jet injectors: energetics of jet formation and penetration.

Abstract

Pressure-driven jets have been used for intradermal delivery of a variety of drugs. Despite their introduction into clinical medicine, variability and occasional bruising have limited their widespread acceptance. Although numerous clinical studies of jet injectors have been reported in the literature, surprisingly little is known about the mechanisms of jet penetration into the skin. In this article, we report results of our studies aimed at determining the dependence of drug delivery on jet velocity and diameter. These studies were performed using two experimental models, porcine skin and human skin. Our rationale for using two models was to explore the possibility of using porcine skin as a model for human skin. Dermal penetration of jets possessing a range of diameters from 76 microm to 559 microm and a range of velocities from 80 m/s to 190 m/s was studied into human and porcine skin. Penetration was quantified using radiolabeled mannitol. Pressure and velocity of the jets were measured using a calibrated pressure transducer and high-speed photography. Penetration of the jet into the skin was determined by two main parameters, jet diameter and average jet velocity. Substantial variation in jet penetration into porcine skin was observed for skin pieces obtained from different anatomic locations. For porcine skin, a parabolic dependence of jet delivery on velocity and diameter was observed. The threshold velocity is suggested to be between 80 and 100 m/s for a jet diameter of 152 microm. Above the threshold velocity, the delivery increased for velocities up to 150 m/s, after which delivery decreased with increasing velocity. At a constant velocity of 150 m/s, jet delivery exhibited a maximum at a diameter of 152 microm. Results obtained with human skin were qualitatively similar but quantitatively different. The threshold velocity for jet penetration into human skin was comparable with that in porcine skin; however, the maxima observed in jet delivery into porcine skin with respect to jet velocity was not apparent for human skin over the range of velocities explored. These studies offer a quantitative analysis of jet penetration into the skin.