Articles

Innovative drug delivery solutions

The driving factor behind TransDermal Technologies’ range of products and solutions was a desire to advance drug delivery technology, Kenneth Kirby, Founder, President and Chief Executive Officer explained to Partnering Focus. The improved technology, a rapid drug delivery system, delivers drugs either in semi-solid or liquid form directly through the skin.

TransDermal Technologies originally began as an over the counter products company in 1990. Penetran, its first licensed product, is a quaternary ammonium active topical analgesic that is used to treat pain associated with arthritis, tendinitis, bursitis, muscle strains and minor bruises. “Going to market with Penetran gave the company profitable exposure on a national scale,” according to Mr. Kirby.

The company was approached by a biochemist who was interested in the concept of delivering drugs without the limitations of a patch. Combining this idea with its Penetran technology, TransDermal Technologies began analysis of existing transdermal drug delivery systems to provide targets for future research. Issues with existing products include:

• speed of delivery—the drug needs to move quickly through the skin to reduce drug metabolism and immune response
• size of molecule and amount of drug delivered—patches can only deliver compounds less than 320 Da that are effective at low doses
• irritation—the drug and patch or gel should cause minimal irritation to skin.

“So how to move on from here—the limitations of existing transdermal systems are to do with interactions of drug and solvent with the patch reservoir materials, so eliminate the patch and reduce the challenges!” Mr. Kirby explained.

Research began on the mechanism of action of Penetran, and the small list of agents with potential to travel through the skin via a conventional delivery system. Since then, the company has completed a number of pre-clinical and clinical trials with hard-to-deliver drugs and has more than five years’ sales of Penetran+Plus, its TDS-enhanced product, under its belt.

The company was granted U.S. Patent 6,444,234 in September, 2002 citing no prior art and just last month received notice that claims had been allowed on a second TDS® patent. Two additional patents are pending.

The TransDermal Technologies TDS® delivery technology is a dose of the drug compounded into a liquid or semi-solid vehicle applied directly to the skin using a metered pump, and has many advantages that contribute to enhance existing drug products and spark interest from potential partners:

• Vehicle is non-toxic and non-irritating
• Improves drug safety and decreases side-effects.
• Reduces dose size (compared with oral administration) by bypassing stomach and liver.
• Supports synthesis of a range of new effectively administered products
• Allow the movement of a number of different sized molecules (up to 1500 kDa) and doses (up to 200 mg/cc) through the skin by reversibly altering the skin structure.
• Allows flexibility of dose titration for age and weight.
• Increases compliance.
• Allows pediatric use.
• Reduces production costs.
• Uses ingredients ‘generally regarded as safe’, in their own right lowering regulatory compliance concerns.
• Enables rapid estimation of feasibility of application to a particular drug• Is very inexpensive to produce and is readily scaled up.

TransDermal Technologies’ patented Molecular Evaluation System computer protocols facilitate rapid development of the final formulation, by producing an accurate ‘recipe’, based on the drug attractive and repulsive forces, dosage and activities. This pioneering technology generally predicts an optimum formula as a result of its calculations and can be used as is, or only requires one or two refining iterations, for example when dealing with semi-solid drugs that are harder to deliver transdermally.

Current products in the pipeline include a testosterone hormone replacement drug. This market has seen an explosion in sales in the United States since the introduction of the leading gel formulation three years ago, and is valued at around US$300 million. Existing testosterone gel drug products have many disadvantages; including that for five hours after administration patients must avoid others touching the skin application area, swimming or showering; and the discarded packaging can contain enough testosterone to potentially harm a small animal.

Trials are ongoing to assess the pharmacokinetics and bioavailability of the product which are believed to be more nearly aligned with the natural pulsatile curves. This more natural dosing, the expected rapid skin absorption of the drug (90% of the testosterone is absorbed after 30 minutes) and the ability to tailor the dose to patient needs should put the TDS® Testosterone product ahead of its competition in reduced safety concerns, ease of use and dosing flexibility.

The company also has promising preclinical data on seven other products, including an antihistamine product that is effective within 2 minutes of application and several non-steroidal anti-inflammatory drugs aimed at the more commercial side of the pharmaceutical sector.

Potential applications of this drug delivery technology are endless; a number of current marketed and off patent drugs could benefit from employing its technique. For these collaborations, TransDermal Technologies will mainly use the service business model, supplying the development and sole use of the delivery system/drug for a fee, partnering with the client through the preclinical and clinical research; although in certain circumstances TransDermal Technologies may be interested in developing the applications up to a pre-agreed milestone and then handing them off to a licensee and in others, continuing involvement beyond approval through providing manufacturing of the finished product.

Current license option collaborations include a three molecule deal with an undisclosed company, and a peptide agreement with another. TransDermal Technologies has an ongoing research collaboration with the Department of Experimental Pathology of the William Harvey Institute of St. Bartholomew’s and the Royal London School of Medicine and Dentistry (London, UK) for preclinical and clinical development through a charitable related entity.

With four OTC products on the market (Penetran, Penetran Plus, Progest Plus and Cellulex), and a little strategic investment from angel investors, TransDermal Technologies is safely funded to support its ongoing research. Additional investment may spur taking several of the molecules proven in the pre-clinical models into clinical trials and thereby increasing the value of the application.

So what else is in store for this company? Ideally, growth into a solutions resource company that out-licenses its technology rates first on the list. Enlargement of the company via out-licensing would dramatically increase profits and drug+TDS production will further enhance profitability which in turn would provide more incentive for potential investors, and partners in the technology wishing to invest and share resources.

Details at http://pharmalicensing.com/company/dispcompany/2252

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