New technologies, needs will spur transdermal/transmucosal delivery

According to the latest in Kalorama Information's series of reports on drug delivery markets, worldwide revenues from transdermal/transmucosal therapies climbed by around 1.5 per cent year on year to $6.86bn in 2006.

They are expected to continue increasing at roughly 3.5 per cent a year to reach $7.9bn by 2010, driven in particular by sustained growth of biotechnology drugs that call for novel delivery technologies; ageing populations with a need for easier and more controlled modes of administration; innovation in materials; and the rapid emergence of transmucosal therapies with as much as four times the absorption rate of drugs delivered through the skin.

While transmucosal products are a relatively new drug delivery strategy, transdermal drugs have carved out a well-established niche since the introduction of the first patch formulations, Transderm-Scop (scopolamine) and Transderm-Nitro (nitroglycerin, both Alza), in 1981.

A number of transdermal drugs followed in their wake, such as Catapress-TTS (clonidine, Boehringer Ingelheim), Estraderm (oestradiol, Novartis), Duragesic (fentanyl, Janssen) and in particular nicotine patches, which leveraged their success on prescription into the over-the-counter market.

While patent expiries and subsequent generic competition have now started to cut into revenues of some of the leading transdermal products, such as the adjunctive cancer treatment Duragesic and some of the hormonal therapies, product innovation, patient preference and superior efficacy are expected to keep up the momentum of the key nicotine patch segment.

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Part of the reason for this is that patches are the best method for these nicotine withdrawal medications," comments Mary Ann Crandall, Kalorama analyst and author of the Drug Delivery Markets series.

"Attempts to deliver through nasals sprays have failed, and the lozenges are just terrible … they've been rejected by most patients.

They even tried to make a cherry losenge, but that didn't work.

Improved patch design - especially in the area of new adhesives and compound improvements will keep this a robust area of transdermal drug delivery."

All the same, patent expiries in general will be a damper on growth, Crandall believes.

Kalorma's figures show a substantial hike in revenues from transdermal/transmucosal drugs between 2003 and 2004, by 14.5 per cent to around $6.3bn, followed by growth of 6.3 per cent to $6.7bn in 2005.

Since then, though, year-to-year increases have been more modest.

Furthermore, the transdermal drug delivery category specifically, which accounted for the bulk ($5.7bn) of the overall transdermal/transmucosal market in 2006, is expected to grow at just 0.5 per cent per year over the forecast period, reaching $5.9bn.

The transmucosal category, on the other hand, which was worth around just $1.2bn last year, is forecast to hit $2bn by 2010.

"Transmuscosal shows promise because it has four times the absorption rate of skin, perhaps even more: it varies somewhat from person to person," comments Crandall.

Two examples are Generex' flagship Oral-lyn, a liquid formulation of regular human insulin delivered to the buccal mucosa by means of the RapidMist device, a spray that limits absorption to the mouth with no entry into the lungs; and Cephalon's Fentora, a tablet formulation of fentanyl for the management of breakthrough pain in patients with cancer who are already receiving and are tolerant to opioid therapy .

Technological advances in the materials used for transdermal/transmucosal delivery will also continue to be a crucial growth factor, Crandall predicts.

"In transdermal delivery, adhesives are the area that presents the most challenges but also the most opportunities to the company that can solve them for the most customers," she adds "Patients in some cases can have negative reactions to the adhesive, which would rule out patches as a delivery method for them until another combination comes to market."

As the report notes, a drug's solubility is another critical feature of transdermal system design: "If solubility in an adhesive is too low, it may not be possible to formulate the required dose (unless other solubilisers are added), or the formulation may be unstable and susceptible to crystallisation over time.

If drug solubility is too high, the rate of drug delivery may be reduced."

3M has addressed this problem by developing 'custom affinity adhesives', which can be tailored to the characteristics of an active drug ingredient in order to achieve optimum solubility levels.

Increased solubility allows a larger drug dose to be administered, at a higher rate and with an extended duration of delivery.

According to the Kalorama report, there is "no potential limit" to the therapeutic categories that could be enhanced through transdermal systems, although some have a particular affinity for this form of delivery, such as sex hormones and pain management.

The potential benefits include continuous, controlled release and absorption of the drug into the body, avoiding the pre-systemic metabolism that may occur after oral dosing; improving patient compliance by offering more convenient dosing regimens; and the ability to discontinue treatment rapidly by removal of the delivery system.

In some cases, though, the dominance of orally administered products has limited entry and better acceptance of transdermal formats.

Oestrogen/progestin products are one area where the benefits of transdermal delivery "are not well understood".

As Crandall points out, "these products have suffered due to problems with absorption into the skin barrier … chemical reactions to the adhesives are problems for these patches as well as other patches."

A potential solution is VIVUS' Evamist, a once-daily transdermal spray that delivers oestradiol for the treatment of hot flashes in women.

The product, which uses Acrux' drug delivery technology, has been filed for approval with the US Food and Drug Administration (FDA).

Technology market The market for drug delivery technology alone in the transdermal/transmucosal categories expanded by an average 6.3 per cent a year from $364m in 2002 to $464m in 2006, the report says.

Given the added value offered by drug delivery systems to pharmaceutical companies in expanding markets and indications or extending product life cycles, the technology-alone portion of transdermal/transmucosal sales is expected to reach $594m by 2010.