Iontophoresis involves the active transportation of a drug into the skin using a constant low-voltage direct current. Ions migrate between electrodes of opposite charges, promoting ion transport through the skin () [29
]. A direct electrical current facilitates the dermal penetration of positively charged lignocaine molecules when placed under a positive electrode for local anaesthesia. Physicochemical properties, such as good aqueous solubility, and the presence of charged groups that render peptides and proteins “difficult to deliver” by other approaches, are ideal for iontophoresis [30
] The amount of drug delivered via iontophoresis is dependent on the current and the duration of delivery. The control afforded by constant current iontophoresis over transport rates means that peptide/protein delivery kinetics could mimic endogenous secretion profiles [30
]. Moreover, complex input kinetics can be used to optimise and individualise therapy.
Figure 8 Iontophoresis. Components of an anodal iontophoretic device are a current source; a current control device; anode (donor) reservoir system (with a positively charged drug/ion in solution); cathode reservoir system (on a different skin site). With an (more ...)
Iontophoresis has been known to cause skin irritation at higher current densities or upon longer application [16
]. Moreover, when direct current electric field is applied over longer durations, an electrochemical polarisation occurs in the skin which decreases the magnitude of current flow through the skin [16
]. This in turn could affect the amount of drug ions driven across the skin.
Small, portable iontophoresis devices have been developed. Dermal anaesthesia can be achieved fairly rapidly using lignocaine iontophoresis without needles [29
]. Adrenaline added to the lignocaine solution enhances the effect and duration of local anaesthesia during iontophoresis; this is due to the local vasoconstriction inhibiting lignocaine absorption into the systemic circulation.
Delivery can be hastened by using ultrasound. In a Randomised Controlled Trial, ultrasound pretreatment plus two-minute low-voltage iontophoresis provided better skin anaesthesia than sham-ultrasound plus two-minute low-voltage iontophoresis, and similar to standard, 10-minute high-voltage iontophoresis [33
]. Lignocaine HCl 10%/Adrenaline 0.1% topical iontophoretic patch (LidoSite) is the first FDA-approved prefilled active anaesthetic patch. In volunteers, it was found that 2% lidocaine could be delivered up to 5
mm below the surface of the skin when the drug compound contained adrenaline, and when passive delivery occurred for at least 50 minutes after the active delivery has terminated [34