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Delivery of therapeutic pharmaceutical agents across the skin addresses the above- mentioned problems by offering a number of potential advantages compared to conventional methods, such as pills and injections, including: (1) little or no degradation or modification of the pharmaceutical agents such as digestion of the proteins by the enzymes and surfactants resident in the stomach and small intestine; (2) an increase in drug effectiveness as the transdermal route avoids first pass metabolism by the liver; (3) minimization of gastrointestinal and other side effects caused by ingestion of the pharmaceutical agent; (4) an improvement in patient comfort and compliance due to a more user-friendly delivery method; and (5) the potential for prolonged and controlled drug delivery. Current research into transdermal transport of water-soluble molecules focuses on: (1) using chemical enhancers to alter the skin's lipid environment; (2) using liposomes to facilitate transdermal transport; (3) using iontophoresis to provide an electrical driving force for transdermal transport; (4) using electroporation to create a new transdermal pathway; and (5) using ultrasound to create a new transdermal pathway. Although chemical enhancers have been shown to increase transdermal transport of small compounds, they are often shown to cause significant skin irritation and may affect drug stability (Santus et al.

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2000;393(1-3):165-170. Razadyne [package insert].]