More Than Skin Deep

November 1, 2005
Ryan D. Gordon

Pharmaceutical Technology Europe

Pharmaceutical Technology Europe, Pharmaceutical Technology Europe-11-01-2005, Volume 17, Issue 11

Recent advances in transdermal technologies challenge the paradigm that only a few drugs can be delivered transdermally.

The transdermal patch has become a proven technology offering a variety of significant clinical benefits over other dosage forms. Because transdermal drug delivery (TDD) offers sustained drug release, it enables a steady blood-level profile, reducing systemic side-effects and, sometimes, improving efficacy over other dosage forms. In addition, because transdermal patches are user-friendly, convenient, painless and provide multiday dosing, transdermal patches can improve patient compliance. Certainly, TDD is not suited nor clinically justified for all drugs. However, recent improvements in TDD technologies are expected to grow the market by expanding the opportunities available to this dosage form.

The US market for TDD for systemic treatment of chronic illnesses spans 12 molecules, including clonidine, estradiol, ethinyl estradiol, fentanyl, levonorgestrel, nicotine, norelgestromin, norethindrone acetate, nitroglycerin, oxybutynin, scopolamine and testosterone. Since 2001, the US transdermal market has more than doubled, based on product sales. While much of the growth has been from mainstay products such as Duragesic, significant growth has been driven by new product launches, such as OrthoEvra. The launch of this 7-day contraceptive patch provides an example of the benefits that TDD can provide to a relatively mature therapeutic area.

Analysts forecast a double-digit compound annual growth rate for the US transdermal market over the next decade. Products in late stage development should continue to fuel market growth and could expand patch usage into new therapeutic categories, including attention deficit and hyperactivity disorder, depression, Parkinson's disease and female sexual dysfunction. New and improved transdermal products that have launched recently or are under development (such as Climara Pro, Menostar, Duragesic and testosterone gels) could expand the presence of transdermal dosage forms in pain management, osteoporosis and hormone replacement.

Interest exists in expanding the function and capabilities of TDD, with many significant innovations in transdermal technologies occurring over the last decade. The innovations can be separated into two categories: transdermal formulations and transdermal technologies. The former involves passive transdermal delivery, including product design, formulation and components. The latter involves newer transdermal technologies, including microneedles, iontophoresis, sonophoresis, electroporation, laser ablation, thermal energy, RF energy ablation and magnetophoresis.

Recent advances in transdermal technologies challenge the paradigm that only a few drugs can be delivered transdermally. Generally, the best passive transdermal drug candidates are nonionic, low molecular weight (less than 500 Da), slightly lipophilic (log P between 1–3), low melting point (below 200 °C) and potent (dose less than 10 mg per day). However, creative formulating with permeation enhancing excipients enables delivery of molecules that don't have these properties. Also, with the active and micropore-creating transdermal technologies, molecular size, ionization state, solubility and potency are not limiting factors.

A promising transdermal technology for macromolecules is microneedle enhanced delivery. These systems use an array of tiny needle-like structures to create pores in the stratum corneum and facilitate drug transport. One example of this system has plastic needle-like structures that are small enough that they do not penetrate into the dermis and, thus, do not reach the nerve endings, so there is no sensation of pain. Such microneedle systems have been reported to greatly enhance (up to 100000 fold) the permeation of macromolecules through skin. Currently, microneedle systems are being coated with vaccines to directly deliver vaccine to the skin's epidermal layer.

TDD is a proven technology that still offers significant potential for growth, with many new product offerings in the coming years. Information suggests that more drugs can be delivered transdermally than the 12 that are already on the market. However, next generation technologies will enable even broader application of TDD to the pharmaceutical industry. Technologies such as the use of microneedles for delivery of vaccines will reshape the way we think about TDD, and open up the benefits of this dosage form to a wider range of therapeutic areas.

Ryan D. Gordon is product development specialist at 3M, St Paul, MN, USA.