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 3
The device consists of a handheld electronic control unit and a microelectrode array. The control unit (see Figure 2a) is battery-operated, rechargeable, and reusable for at least 1000 applications. This particular device is available in three sizes (treatment area of 1, 2.5, or 5 cm2 ), depending on the desired dose of drug to be delivered (see Figure 3).


Figure 4
The microelectrode array (see Figure 2b) contains hundreds of microelectrodes. The microelectrode array is disposable, low-cost and intended for one use only. The array is based on a proprietary design and made of biocompatible materials that are well-established in medical devices. Within a few seconds, the control unit and the array create an array of RF microchannels (see Figure 4), thereby preparing the treatment site for the patch containing the drug. After application of the patch (see Figure 2c) on the pretreated area, the drug passively diffuses from the patch through the RF microchannels into the inner layers of the skin and into systemic circulation (9).

Patch technology for protein delivery


Figure 5
Transdermal delivery of large proteins is a novel and exciting method (10). No commercial technology currently available incorporates proteins into transdermal patches. The unique printed-patch technology for transdermal delivery of proteins complements RF cell ablation. The manufacturing method involves dispensing very small droplets of a concentrated protein solution on a transdermal liner in a predetermined pattern (see Figure 5). The liquid is dried, leaving a dry and thin layer of formulated protein on top of the liner. The highly water-soluble proteins are dissolved by the interstitial fluid that is secreted from the skin through the RF microchannels, thus forming a highly concentrated protein solution in situ. The diffusion of the dissolved molecules occurs through the RF microchannels into the viable tissues of the skin across a steep concentration gradient. This process brings about a high delivery rate and a peak-blood profile of the drug resembling that of a subcutaneous injection (9).

A dispensing–manufacturing technology widely used in the diagnostic industry was adapted to successfully manufacture the printed patches. This manufacturing method enables complete and flexible control of the drug load on the patch, control of patch size and shape, and high manufacturing yield with minimal protein losses. In addition, this method fully retains the stability and biological activity of the protein drug. Printed patches were used in studies in which human growth hormone, insulin, and teriparatide (hPTH1–34) were delivered in animals (guinea pigs and pigs) and humans (11).


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