Advances in Radio-Frequency Transdermal Drug Delivery - Pharmaceutical Technology

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Advances in Radio-Frequency Transdermal Drug Delivery
A microelectronic system based on radio-frequency (RF) cell ablation addresses limitations of other transdermal drug-delivery methods. This system expands the transdermal spectrum to include the delivery of water-soluble molecules, peptides, proteins, and other macromolecules.

Pharmaceutical Technology

Figure 8
It is possible to achieve a sustained drug flux for 24 h by incorporating the active material into a moist matrix such as a hydrogel that serves as an infinite reservoir. The matrix holds the drug on the skin in a soluble form, which makes it available for delivery through the aqueous microchannels. The matrix releases the drug slowly at a rate suitable for delivery, enabling the drug concentration in the blood to be maintained as long as 24 h. This effect was shown in a human study of granisetron delivery. The study measured the transdermal delivery of granisetron (a charged, water-soluble molecule) during a period of 24 h. The drug was administered through a small patch (5.6 cm2 ) using a microelectronic system based on RF cell ablation (the ViaDerm system). This delivery method was compared with other routes, including passive transdermal delivery, oral delivery (one tablet every 12 h), and intravenous (IV) delivery. The study was conducted on six healthy adult volunteers in each test group. The results (see Figure 8) revealed differences in the plasma-drug levels and profiles between the treatments. The IV and oral deliveries displayed a peak or peak-and-valley profile corresponding to the administration regimen. In contrast, the transdermal delivery through microchannels resulted in a concentration increase up to 9 h and a constant level up to 24 h, indicating that the channels enabled drug delivery for at least 24 h. The control group (marked as "ViaDerm untreated" in Figure 8) showed very low plasma levels across the entire time period, emphasizing that the skin pretreatment used to form microchannels enabled the transdermal delivery of this water-soluble molecule.

The variability in drug levels in the blood of subjects treated with the system using RF cell ablation was similar to that measured for oral delivery. This finding confirms that RF microchannel formation is uniform and reproducible.

Factors influencing bioavailability and delivered dose

Table II
A large delivered dose and high bioavailability are important for any drug-delivery method, particularly for costly macromolecule active materials. If the bioavailability of the protein using a specific delivery method is low (< 10–20%), there is a significant loss of protein. Alternative delivery routes for peptides and proteins result in low bioavailability compared with subcutaneous injection (12). A microelectronic system based on RF cell ablation using printed-protein patches resulted in very high bioavailability of up to 40% relative to subcutaneous injection. Table II shows the bioavailability of three drug molecules. The data show that a low (i.e., 6%) or high (up to 40%) relative bioavailability is attainable, depending on the ratio between the amounts of active material and microchannels.

Drug delivery through microchannels

Drug delivery through microchannels using RF cell ablation may be affected by the molecular size of the molecule delivered, water solubility, concentration, microchannel density, duration of delivery, dosage forms, drug profile, type of patches, and drug accumulation.

Molecular size . No data exist regarding the limitation of the size of drug molecules that can penetrate the microchannels. The transdermal delivery of small-molecule drugs can be increased significantly by pretreatment. In addition, macromolecules such as peptides and proteins can also be delivered systemically through the skin using this technology.

Solubility in water. The microchannels are filled with interstitial fluid. Water-soluble molecules, therefore, can be easily delivered through the microchannels of the inner layers of the skin and by systemic circulation. Water-insoluble drugs can be delivered transdermally using RF cell ablation by increasing the water solubility through a suitable formulation.

Concentration. As in any passive delivery, the rate of delivery depends on the concentration gradient. Increasing the drug concentration on the skin in the vicinity of the microchannels will result in a higher delivery rate.


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