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

Microchannel density. By increasing the microchannel density (MCs/cm2 ), a higher amount of drug can be delivered. This higher amount results in a more efficient delivery process or enables the delivery of a higher one-time dose.

Duration of delivery. The duration in which enhanced drug delivery can be observed is up to 24 h, after which the delivery rate will not be significantly higher compared with delivery using intact skin. The maximum patch application time should be 24 h.

Dosage forms. A patch is the most convenient dosage form to use with the microelectrode system. A patch has a drug area size matching the size of the electrode array. Simpler dosage forms such as gels or creams, however, can also be used. Also, the delivery of the drug in semisolid-dosage forms on treated skin can be increased significantly compared with delivery on intact skin.

Drug profile . The result of the transdermal delivery using RF cell ablation can be a peak-plasma profile or a constant blood level, depending on the type of patch technology used.

Type of patches. A reservoir patch, usually a water-based hydrogel, can be used to incorporate small or large molecules and apply them on the skin. A hydrogel patch maintains the skin in a hydrated state, and therefore enables drug delivery at a constant level for up to 24 h. For proteins, the use of a printed patch is advisable for stability purposes. The resulting blood profile is in a peak shape that resembles that of an injection. The use of printed patches also results in efficient and cost-effective delivery.

Lack of reservoir in the skin. One of the most disturbing issues regarding passive delivery is the accumulation of drug in the stratum corneum because of the affinity between hydrophobic drugs and this lipidic tissue. A drug in the reservoir continues to be released into circulation long after the treatment stops, thereby decreasing the effectiveness of the treatment. The microelectronic system based on RF cell ablation used in this study delivered water-soluble drugs that cannot be accumulated in the lipidic stratum corneum. No issue of reservoir formation exists.

Other transdermal drug delivery technologies

Drug delivery using a microelectronic system based on RF cell ablation offers a convenient, painless, and less invasive alternative to injection, a common method for administering large proteins and peptides. This system also allows for less costly manufacturing that may not require sterility or expensive processes such as lyophilization. In instances where multiple daily administrations are needed, the one-a-day application based on RF cell ablation avoids the need for multiple injections or continuous infusion.

Although injection is the primary delivery method for large-molecule drugs, small molecules may also be delivered orally or through passive transdermal methods. Oral drug delivery methods suffer from low gastrointestinal (GI) absorption and high first-pass effect, which may lead to low oral bioavailability and potential adverse GI effects. A transdermal alternative overcomes these limitations and offers the benefit of immediate cessation of drug administration in case of an adverse effect or overdose. Transdermal delivery also enables verification if a drug were taken or not, thereby improving compliance and monitoring in dependent populations such as dementia patients.

Although passive transdermal delivery methods provide these benefits, they do not allow for the delivery of water-soluble drugs, a capability inherent in RF cell ablation. As earlier discussed, passive transdermal delivery often leads to the formation of a drug reservoir in the stratum corneum because of the affinity of the lipophilic active drug to the stratum corneum. The buildup of this reservoir results in a long lag time before therapeutic concentrations in circulation are reached, a problematic titration process, as well as a long elimination process in treatment termination. RF cell ablation overcomes this problem because of the hydrophilic nature of the drugs it is able to deliver.


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