Advances in Transdermal Technologies

Transdermal delivery takes up once-forbidden compounds, reviving markets and creating formulation opportunities.
Oct 02, 2007
Volume 31, Issue 10

During the past 20 years, the transdermal delivery systems (TDDS) have greatly expanded their role in healthcare, fueled primarily by their advantages over other routes of administration. TDDS avoid the first-pass metabolic effects of the liver, ensure compliance, provide steady sustained release, and reduce pill burden. In addition to the first TDDS products on the market, including estradiol, nicotine, and combination hormone replacement therapies, a range of other products have been approved in only the past two years (see Table I).

Passive delivery

Table I: Recently approved transdermal drug delivery systems.
Passive TDDS have been used for decades to successfully deliver small-molecule drugs. Since the first reservoir patch was developed, there have been several advancements to passive-diffusion formulations, most notably the one-layer drug-in-adhesive (DIA) technology (see Figure 1). Unlike the liquid-in-a-pouch reservoir, the DIA matrix is solid and therefore does not have a potential for leakage. Advancements in the DIA technology include the ability to deliver more than one drug in one patch.

Figure 1: Drug in reservoir and drug in adhesive designs. (FIGURE: ADHESIVES RESEARCH)
Passive TDDS are applicable for lipophilic, low molecular weight (< 500 Da) molecules or molecules that have fairly low doses. Various combinations of permeation enhancers and other excipients in passive TDDS have been used for molecules with slightly larger molecular weights or higher doses. The type of enhancer depends on its compatibility with the drug and its permeability, and the rate of diffusion depends on the skin and TDDS membranes. Even with the use of enhancers, however, there is a limited number of drugs for which the passive delivery method can be used.

Nonetheless, a passive delivery system generally is preferred over an active system because it is more marketable, less expensive to manufacture, and it does not involve a third-party company for the electronics or other device components. In addition, some patients are uneasy about having active delivery TDDS on their skin for any period of time.

Active delivery

The transdermal market is progressing toward active methods of drug delivery. "The expansion of this market includes the incorporation of technologies that address the limitation of the molecule size as well as the desire to enhance dosing accuracy and control. Research in these areas is increasing rapidly," says Richard Sitz, technical manager, Transdermal Drug Delivery, 3M Drug Delivery Systems Division (St. Paul, MN).

Figure 2: Microneedle system. (FIGURE: 3M)
For example, 3M developed a "Microstructured Transdermal System" (MTS), which is a microneedle system for transcutaneous or intradermal drug delivery (see Figure 2). "MTS bypasses the barrier properties of the stratum corneum and provides a means to deliver various molecules such as vaccines or macromolecules, that ordinarily would not penetrate the skin," says Sitz.

Other TDDS use an energy source such as electricity (iontophoresis) or heat to enhance permeation. Although there are several heat-assisted systems in development, not one has yet been approved. "The advances in active delivery technologies are very exciting. Once these technologies pass regulatory scrutiny, more transdermal medications will be available for patients," predicts Carolyn Myers, president of Mylan Technologies (Burlington, VT). Recent approvals in TDDS include an iontophoretic unit (see Table I).

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