- The Washington Times - Tuesday, December 10, 2002

The small medical patch is slowly but surely having a big impact on drug and analgesic delivery methods. It's even helping improve the efficacy of at least one medication, making it superior to the pill form.
According to a November report in the American Journal of Psychiatry, a recent clinical study has shown the patch to be more effective than pills in treating major depression.
When taken orally, the medicine an enzyme inhibitor called selegiline was liable to cause severe side effects in patients, largely because it interacted badly with certain foods in the digestive system. Applied to the skin, a patch delivered the same drug into the central nervous system instead of the digestive system, thereby avoiding complications.
The humble patch, more correctly known as a transdermal delivery system, has been around for 20 years, but researchers slowly and surely are exploring new and better ways of applying the device.
Ongoing trials indicate the patch is about to enter a new phase as well especially in the area of pain relief. The California-based Alza Corp., whose parent company is Johnson & Johnson, is developing what is known as an "active" patch that allows a user to control the flow of anti-pain medicine with the help of an electronic button similar to the pump that post-operative patients use to control doses of morphine.
Registered as E-Trans, (e for electronic and trans for transdermal), the projected patch is the size of a credit card slightly larger than conventional-size patches, which generally are 13/4 inches round.
Advocates of patch delivery systems say a pill goes to the liver first, so a lot of the drug gets broken down and metabolized first through the digestive system. The skin metabolizes a substance faster, so the amount of drug needed is less in a transdermal system.
Most conventional patches deliver the drug slowly, whereas with tablets, the body gets a spike before the drug is broken down.
Depending on the manufacturer, patches are either clear or opaque.
A patch may take longer to relieve symptoms, but because it does not require daily administration, a person is less likely to forget his or her dosage. Thus, effectiveness can be assured, and the problem of compliance which often what occurs with patients suffering from depression is overcome.
Undoubtedly, most people would prefer a patch or pill over an intravenous drip or periodic injections. To date, such choices are not possible in most areas of medicine either because of the state of technology or, more often, the chemical makeup of the drug.
Alza also is developing a method it calls Macroflux transdermal technology, which it says will penetrate the skin more deeply using what Howie Rosen, Alza's vice president of product development, describes as an array of precision microprojections in a special patch using an applicator.
Neither of the above designs are yet on the market. While promising, they are several years away from being commercially available.
The introduction earlier this year of the first weekly contraceptive patch, called Ortho Evra, was a breakthrough of sorts in convenience for women practicing birth control because it relieves them from having to remember to take a daily pill. It was the first such patch to receive the approval of the U.S. Food and Drug Administration.
Worn for one week at a time and replaced the same day of the week for three consecutive weeks, the contraceptive patch as developed by Johnson & Johnson and marketed by Ortho-McNeil can be worn in four areas of the body. The area chosen weekly can be either the buttocks, the abdomen, upper torso (excluding the breasts) or upper outer arm.
That is just the latest in a number of patch devices available from a range of pharmaceutical companies. In addition to birth control, there are therapeutical patches for hormone replacement estrogen for women and testosterone for men; nitroglycerin patches for angina patients; scopolamine to relieve motion sickness; and fentanyl to manage chronic pain.
Dr. David Downing, an obstetrician-gynecologist at Washington Hospital Center, has recommended the hormonal patch for seven to eight years as an option over the pill. He estimates that hormone replacement therapy (HRT) in patch form is used by 15 percent of his patients compared to 85 percent using pills.
Using a pain-relieving patch that is effective for three days at a time is the equivalent of taking one to six painkilling pills a day, says Dr. Lee Ann Rhodes, medical director of pain management at Washington Hospital Center. Much depends on the individual patient, she says.
Scientists keep exploring possibilities for using the patch for such diseases as osteoporosis. (To date, only an injectable version of a palliative drug for osteoporosis from the Eli Lilly Co. has been approved by the FDA.)
The challenge is in finding drugs or combinations of liquids that go through the skin without difficulty. Chemical enhancers such as alcohol are used to help in some cases because it turns out that alcohol goes through the skin well, as does nicotine.
The chief difficulty involved is the size of molecules in the drug relative to the strength needed to be effective. Patches work by slow-release diffusion of a substance through the skin. Their application is limited depending on the chemicals involved and occasionally by the thickness of the skin.
That helps explain why finding new delivery methods is difficult as well as important. The skin is the body's protective agent, helping keep things out.
"We found if you can get through the dead layer on top which provides the most resistance to drugs going through you can get a lot more drugs into the body," says Alza's Mr. Rosen. Hence the development of the Macroflux system, which uses microprojections to push through more potent drugs.
"These [microprojections] are long enough to get through the dead layer, but not so they cause pain," he says. "If you rub the surface of the patch, it feels like fine sandpaper."
The most promising future for this method is its use with vaccines to eliminate needles, Mr. Rosen says. "It turns out that we have a lot of immune cells in our skin. If you can put vaccine in the skin near the immune cells, you get a longer protection," he says.
There probably are fewer than 10 drugs in patches on the market, compared to 3,000 or more sold in the United States, Mr. Rosen notes, because "you have to be able to get enough through the skin to be effective."
Another challenge, he notes, is "if you give someone the wrong amount of a drug, such as insulin [for diabetes sufferers], you can kill them. Insulin is a pretty large molecule, so it's hard to get through the skin."
The most profitable patch to date for the Alza Corp., which claims to have introduced the concept of controlled transdermal delivery, is the Duragesic patch used widely by prescription only to deliver fentanyl for cancer patients and people with severe lower back pain.
In terms of numbers sold, probably the best-known and most popular is the over-the-counter nicotine patch to help smokers stop or curtail their habit. Depending on the degree of dependence, a person trying to end the habit normally will choose patches containing decreasing amounts of nicotine and ease off gradually until none is needed.
The patches are adhesive and unaffected by extremes of body movement or exposure. A rate-controlling membrane that meters out the drug is included in some models .
Cutting a patch and applying only one part at a time as a way of saving money isn't a good idea because the effectiveness is reduced and, in some cases, it can make the patch ineffective. The cost of patches is relatively equal to that of pills except that few patches are generic and therefore less expensive when bought at a pharmacy.
Dr. Michael Zasloff, dean of research at Georgetown Medical Center, agrees that the Alza Corp. is "probably the leader" in this area, but he has some cautionary words to offer about transdermal delivery methods in general.
"Basically, the whole point of a patch really is to provide a more regulated release of a substance than would otherwise be available by ingestion," Dr. Zasloff says. "It is slower, but the biggest challenge is the limitations on the amount of a substance that can actually be delivered in a patch. Even with a huge patch, there is a limitation. You could not administer an antibiotic because the patch form isn't potent enough. Right now, it is limited to delivery of substances that have to be administered in amounts no greater than a few milligrams a day.
"Take Prozac for example. A dose of Prozac exceeds on the average 20 milligrams, which makes it very difficult [to deliver by patch]. The substances most widely used are those like nicotine that are quite potent, which means the amount of chemical it takes to produce an effect is terribly small.
"All things are possible, but it depends. The patch only provides a way of entering the body. It has other problems, because you have to make certain the thickness of the skin is the same and circulation of blood flow is the same one person to the next. It's dangerous if you realize the variation that exists in people. You are dealing with what might affect absorption from skin into the capillaries, which are the blood vessels under the skin.
"Patches are not fundamentally different from an IV, but they are slower. When you take something by mouth, most drugs are first routed via the gut to the liver, which serves as gatekeeper. Intravenously, it has a shot at spreading through body before the liver. What is critical is the liver then doesn't have a crack at [the drugs] to destroy them first."

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