Existing technology for delivering drugs onto and across the skin can be broken
down into two categories: patch or plaster-based and hydroalcohol gel systems.

Patches were developed in the late 1960s and early 1970s and have been successfully
commercialized for a small number of compounds which share the common
characteristics of being:

1. Smaller in molecular weight than about 320 Daltons;
2. Readily soluble in alcohol and;
3. Effective at a dose of less than a milligram in 24 hours.

Drugs such as Scopolamine for motion sickness, estrogen and, less successfully
testosterone, for hormone replacement, and Fentanyl® for pain have been
delivered by patch.

Hydroalcohol gel systems were developed in the early 1980s by a European-based
company and so far have been limited in application to hormone replacement therapy
and some topical “stays in the skin” drug applications.

Recent research on transdermal delivery has identified that the only effective way to
increase the flux of drug across the skin is by adding energy. This has been attempted
by means of mechanisms to heat the patch, circuits to electrify the skin beneath the
patch and even piercing the epidermis with arrays of micro needles. So far, none of
these techniques has been successfully commercialized.

The TDS® incorporates chemical energy into its formulations by maximizing enzyme
substrate. TTI believes that this added energy both assists the viable skin in actively
transporting the complex of drug and vehicle and then recovering from the disruption
as well as maximizing uptake of the drug by its receptors once delivered.

We believe that this patented inclusion of energy into the TDS® has made the
incremental improvement that will take transdermal delivery to the next level.