The majority of currently approved transdermal drug delivery systems utilise low doses of low molecular weight lipophilic drugs, falling within the category of first generation approaches. Systems incorporating improvements such as chemical enhancers, heat, iontophoresis and non-cavitational ultrasound to reversibly disrupt the structure of the stratum corneum, fall under second generation approaches. Although heat is a somewhat uncommon and perhaps understudied enhancement technique, there is considerable evidence to suggest that it can significantly increase epidermal penetration. Given the tolerable nature of these temperatures, there is a clear opportunity for heat assisted absorption to be incorporated into future transdermal drug delivery systems. The use of heat has been shown to increase the rate of transdermal drug delivery in a number of applications, such as administration of fentanyl and lidocaine. The aim of the present project has been to investigate the development of a hybrid smart patch system, which involves the integration of transdermal heat transfer with iontophoresis. This would enable enhanced drug delivery to be achieved in a controlled manner without significant disruption to the skin’s structure.

Iontophoresis provides a mechanism through which delivery rate may be controlled to a high degree of specificity. It is therefore possible to regulate or inhibit delivery rate over a period of time, due to the direct relationship between the applied current and transdermal flux. Rate control may be the responsibility of the patient, or more commonly, controlled by incorporation of a microprocessor, enabling complex and bespoke delivery profiles to be enacted. The addition of the transdermal heater, in this instance, brings a new dimension to the delivery process, but there remains a considerable challenge to the design and implementation of the proposed smart patch.

The basic approach is outlined in Figure 1. In order to address the issue of controlled release and subsequent flux, the design incorporates a temperature sensitive hydrogel as a drug entrapment matrix or reservoir. Hydrogels have traditionally been employed as a barrier mechanism or encapsulation medium in a number of drug delivery studies, where their manipulation and/or degradation may be controlled by environmental influences, hydrolysis and enzyme interaction. In this prototype, thermal control (typically 45^oC) facilities the release of drug from the gel, and its subsequent transfer across the stratum corneum is induced through the combination of heat and iontophoresis.

The design of the microheater / iontophoretic electrode assembly is described and its operation characterised. The drug delivery profiles from prototype smart patches employing a range of model drugs are critically assessed. The extent to which precise control and augmentation of both the release and transdermal delivery rate, for a range of drug species and therapeutic agents has been assessed.