No abstract

Skin forms a protective barrier to the entry of foreign molecules, especially water soluble compounds. Iontophoresis, one of the promising approaches to deliver water soluble drugs through the skin, has already been approved by FDA to deliver lidocaine and fentanyl. Iontophoresis involves application of current (< 0.5 mA/cm(2)) to push charged molecules into, or across the body tissue and offers programmable delivery. This technique encompasses various fields such as developing a device, sophistication of the device, electrode design, electronics and formulation. In addition, combination strategies with other enhancement techniques, is also gaining importance. The focus of this review is on the latest developments in the field of iontophoresis including trends in device development, electrode design, formulation and therapeutic applications as described in the patent literature.

A self-contained Wearable Electronic Disposable Drug Delivery (WEDD ® ) patch was used to demonstrate that diclofenac levels delivered by iontophoresis are greater than estimated minimal effective concentrations in local subcutaneous tissue and are also greater than either passive transdermal or intravenous delivery using hairless rats. In vitro iontophoretic delivery was evaluated to optimize donor cell formulation using Franz diffusion cells and 1000 NMWL Millipore ultrafiltration membrane. In vivo animal studies were done using patches powered with a 4-volt system, consisting of a 1-volt Zn anode and Ag/AgCl cathode with built in 3-volt lithium battery. Blood and microdialysis samples were collected at different time points after patch application. Current levels increased to 1.0 mA at 30 min, then fell to a steady state of ~ 0.4 mA. Both WEDD ® and passive patches produced measurable levels of diclofenac in the subcutaneous tissue below the application site (C max ± SE = 113.3 ± 61.7 ng/mL and 36.3 ± 15.9 ng/mL, respectively). The dose delivered in six hours was calculated to be 0.226 ± 0.072 mg and 0.430 ± 0.048 mg in passive and iontophoretic delivery, respectively. Diclofenac was not detected in the subcutaneous tissue after intravenous administration of 1.5 mg/kg diclofenac solution. The trend indicates that WEDD ® can be used to successfully deliver diclofenac to subcutaneous tissue to concentrations higher when compared to either passive delivery or intravenous dosing of 1.5 mg/kg.

In conclusion, hanging drop is a very easy and effective approach to screen protein formulations in the early stage of formulation development.

Subcutaneous levels of daniplestim were measured following iontophoresis after improving recovery and minimizing fluid loss from the microdialysis probe.