Future of the transdermal drug delivery market--have we barely touched the surface?

INTRODUCTION: Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. AREAS COVERED: This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. EXPERT OPINION: Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

The effect of formulation excipients on the penetration and lateral diffusion of ibuprofen on and within the stratum corneum following topical application to humans.

Distribution profiles of topically applied drugs can be influenced by the presence of excipients. This study investigated the effect of common topical excipients on the simultaneous lateral diffusion and stratum corneum (SC) penetration of a model compound, ibuprofen (IBU) in humans. IBU solutions with and without propylene glycol (PG), polyethylene glycol 200 (PEG 200), and/or octisalate (OS) were dosed onto the forearm of participants. At various times, 10 "tape-strippings" were obtained with perforated concentric tapes and analyzed for IBU concentration and SC protein mass. Complimentary in vitro permeation studies assessed the effect of excipients on the percutaneous absorption of IBU across human skin. Following in vivo application, IBU displayed a greater tendency for lateral diffusion when applied with OS, whereas IBU resisted lateral diffusion when dosed with PG and PEG 200. After 24 h, 25.3 ± 8.0% and 55.5 ± 18.6% of IBU was recovered from the SC in vivo with and without excipients, respectively. There was a twofold-to threefold enhancement in IBU flux in vitro when applied with excipients. The lower IBU recovery from the SC when applied with excipients may be attributed to the permeation enhancement effects of these excipients. The ability of IBU to laterally diffuse appears to be dependent on formulation excipients.

Nanoparticles do not penetrate human skin--a theoretical perspective.

The penetration of intact particles in the nanometer range (nanoparticles, [NP]) through human skin is a controversial topic, which has attracted much interest from both the pharmaceutical and the personal care industries. Concerns have also been raised about the possible implications that dermal exposure to NP may have for human health, particularly from physical sunblock formulations. Here we use a theoretical approach to determine the feasibility of NP penetration of healthy human skin. The maximum flux of NPs of various dimensions is calculated based on two algorithms that have been developed to model passive diffusion of molecules through skin. The results confirm that NPs are too large to permeate skin by this mechanism. Although components of NPs may dissolve in the skin and measurable amounts have been detected in body fluids, this is not indicative of actual NP transport through the skin. The possible roles for NP formulations in drug permeation enhancement are also considered but are not associated with the penetration of intact NP.

A commentary on transdermal drug delivery systems in clinical trials.

The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market.