The Hokunalin Tape jointly developed in 1988 by Abbott Japan Co.

, Ltd and
Nitto Denko was the world's first transdermal patch for treatment of asthma. The
adhesive layer of the tape contains tulobuterol, a drug that dilates the bronchial
tubes making it easier for asthma sufferers to breathe. When the patch is applied
to the skin, the drug penetrates the skin and is absorbed into the blood stream
through the capillaries to flow throughout the body. This is in effect the same as
using an injection, but without requiring the use of a needle.
Unlike conventional oral and inhaled formulations, Hokunalin Tape has the Hokunalin
advantage of being able to appropriately control the concentration of the drug in Tape
the body. This means that users can control asthma attacks, which frequently
occur in the early morning, and that the burden on caregivers is also greatly
reduced.
The development of these patches, however, took 11 years and was full of
challenges.

Chapter 2: Achieving Controlled Drug Delivery was the Greatest Challenge

Designing transdermal patches is one area in which Nitto Denko has

a great deal of expertise. By 1983 we had already developed a
transdermal patch for preventing the onset of angina.

With conventional transdermal formulations, drugs were

continuously in the body for long periods of time. The developers
wanted to develop a more advanced product that was able to deliver
the required drug dosage at the right time for use in the treatment of
The mechanism whereby asthma.
drugs are delivered to the In many cases, asthma attacks occur at set times, such as in the early
body through the morning. If a drug delivery system could be developed that was able
transdermal patch. to deliver the optimum amount of medication at that time (a smart
drug delivery system), then it would be possible to dramatically
increase the quality of life of asthma sufferers.
In order to realize this goal, however, it is necessary to achieve
precision control of drug release speed. This proved to be extremely
difficult.

Chapter 3: Tenacity was required to Solve the Problem of Drug Content and
Concentration Control

Drug release speed is determined by the complex relationships

between the type of adhesive used, the thickness of the adhesive
coating, and the content and concentration of drug contained in the
adhesive. Moreover, the type of adhesive that can be used in A typical scene showing
medical applications is also limited, which means that inevitably it the kind of experiments
is necessary to control release speed using drug content and that were repeatedly
concentration.
In the absence of any revolutionary way of solving this problem, it carried out during
was a matter of making samples with various combinations in a development.
process of trial and error. Although computer simulations can now
be used for parts of this process, at that particular time there was no
such convenience. It was a case of trying every combination and
investigating each individual possibility.
Eventually, as a result of many years of painstaking hard work, this
goal was achieved by utilizing a mechanism whereby some of the
drug in the adhesive was maintained in a crystalline state while the
rest was kept in a dissolved state. This proprietary technology was
subsequently applied in the manufacture of other adhesive tapes.
In order to commercialize this product, however, the company first
had to develop advanced processing technology. In the transdermal
patch manufacturing process, it was necessary to maintain the
thickness of the adhesive layer at 20 (0.02mm). Because the
product was to be used in medical applications there could be no
variation in quality and at the time of manufacture it was necessary
to control tape thickness to within 2m (0.002mm).
It is no exaggeration to say that precision coating technology is the
real secret behind the successfully commercialization of this
product.

Chapter 4: You'll Never Succeed Unless You Try

In order to achieve goals it is necessary to think a lot and then to translate the ideas that come
into action, and to repeat this process time and time again. Basically, manufacturing is a process
that requires you to get your hands dirty and involves much sweat and tears. There is nothing
glamorous about it at all. That is probably one of the reasons that success, when it eventually
comes, is particularly sweet.
At times it may seem as though you are facing a brick wall, but when you get off course you just
have to take the initiative and try something else. Nothing gets solved sitting at a desk.
World-first products do not suddenly appear as a result of some revolutionary idea. The
development of Hokunalin Tape teaches us much about the importance of continually trying
out various ideas and combinations.