Transdermal Patches Are More Than Skin Deep

After modest beginnings, transdermal patches are now taking advantage of nanotechnology and other novel techniques to improve drug delivery.

Transdermal Patches Are More Than Skin Deep

Thomas Morrow, MD
The simply designed transdermal patch has undergone a dramatic transformation over the past decade. In its strictest sense, all transdermal systems attempt to create a balance between a number of key factors including size of patch or coverage area, concentration of the drug, duration of therapeutic drug level, and use of an enhancer.

The advantages of transdermal delivery are obvious — even delivery of a therapeutic level of drug is painless, the patient does not need to inject himself, there are no bulky delivery devices to manage or dangerous needles to dispose of, and there are few or no gastrointestinal effects from the drug itself. Peak plasma levels of the drug are reduced, leading to decreased side effects. In addition, transdermal delivery is useful for those drugs that have a high first pass effect through the liver, have poor oral uptake, need frequent administration, or that interact with stomach acid. The first pass effect results in the destruction of a significant amount of the drug. Drugs absorbed through the skin, however, enter the general circulation directly — avoiding the liver, with less total drug absorption occurring.

These benefits have not been lost on clinicians. As a result, the patch business is growing at a healthy annual revenue rate of 12 percent with a current worldwide market of about $3 billion, with the U.S. making up 56 percent of the market. Unless you are in the transdermal patch business, you will not be aware of the advances under development.

Humble beginnings

The first transdermal systems were simply pieces of plastic dipped into a drug that was dissolved in alcohol. The plastic had an adhesive around the edges. Although revolutionary in their day, they created a significant number of skin reactions, more often than not fell off, and had a number of other limitations. These problems gave a lasting negative impression of the whole sector.

The next generation — still in use today — uses a “drug in the adhesive” model. This is a significant improvement, as the skin irritation is diminished and in many cases eliminated. The adhesive serves two functions: It is the glue that keeps the patch attached to the skin, and it acts as the suspension that holds the drug. But it creates a major challenge: The concentration of the drug within the adhesive directly affects the “stickiness” of the adhesive. Thus, if there is a need for large quantities of drug, either the size of the patch must be increased or the patch needs to be reapplied more frequently. Basically, the patch would not stick, as it would be primarily made up of the drug.

Next generation patches

Third generation patches have solved some of these issues by using an acrylic reservoir that holds the drug. Silicon adhesive is added to create a semisolid suspension of microscopic, concentrated drug cells.

Now, fourth generation transdermal systems involve the addition of an enhancer — a mechanism to increase the permeability of the skin — and in some of the technology, a mechanism to time the delivery and create bolus dosing. There are a number of enhancers to drug delivery. These include iontophoresis, ultrasound, chemicals including gels, microneedles, sonophoresis, lasers, and electroporatic methods.

Some delivery systems avoid the patch altogether. These use a gel that is rubbed into the skin. This method, mastered by Antares Pharma, tailors the kinetic profile of the drug to the gel. CombiGel consists of a hydro alcoholic gel containing a combination of enhancers. This gel is totally invisible and is designed to be rapidly absorbed through the skin. The first transdermal testosterone gel for men, released in 2000, used this approach. The gel was fraught with challenges, including cost, irritancy, delivery efficacy, cosmetic issues, smell, and color. Many other drugs will soon be delivered using this method.

Nanotechnology gaining hold

Another enhancer that is gaining advancement is microneedles. Why should a needle that is a few inches long be used to deliver a drug that is only a few atoms large? This technology combines the advantage of a needle and the transdermal patch.

The devices are dime-sized pieces of polymer with hundreds of hollow microneedles between 100 and 1,000 micrometers long. These small needles penetrate the top layers of skin and allow the drug to pass through with ease. This size of needle does not penetrate deeply enough to stimulate the nerves and hence … no pain!

This technology can be combined with an electronically controlled micropump that delivers the drug at specific times or upon demand. Once approved by the FDA, these devices would allow the patient or physician to control the time and dose of the drug being delivered.

These devices have the potential to place drugs precisely into the area where special immune cells reside, making these drugs capable of modulating the immune system, with relative ease.

Alza is using a slightly different variation on the use of needles. The company has developed the patented Macroflux transdermal technology that uses microprojections to create superficial pathways through the dead skin barrier. The tips of the projections contain active drug — a quick bolus. Interestingly, the Alza Web site displays a study where human growth hormone, a rather large protein, was able to reach therapeutic levels hours after the application of the patch.

Pain relief

Pain relief routinely benefits from transdermal patch technology. Most of the readers are aware of the Duragesic patch. There are several others now on the market. One is Lidoderm, a lidocaine 5 percent patch, which is used for post herpetic neuralgia. Other exciting advancements in pain control include the E-Trans fentanyl HCl patch. This credit card-size patch is an active delivery device that has a self-contained battery that delivers pulses of fentanyl HCl, a strong narcotic.

This mimics the use of intravenous self-controlled analgesic systems that are very expensive, cumbersome, and require considerable nursing care. A study just published in the Journal of the American Medical Association demonstrated that this patch does the job about as well as conventional intravenous devices. Alza is hoping for approval in 2004.

Finally, SonoPrep offers a topical anesthetic system with an ultrasound enhancer. This system uses a small ultrasound generator to transport 4 percent lidocaine HCl into the skin in an area just big enough to place a catheter into a vein or artery. It anesthetizes the area in less than a minute and can allow for prolonged application for several hours.

These advances will revolutionize the delivery of many drugs, enhancing the application of nanotechnology and giving new options to patients needing biologic drugs. Soon, polypeptides and even proteins will not need to be injected or infused.

These advances will soon fuel Tomorrow’s Medicine!

Weight loss with a patch

Weight loss with a patch, WHY?

The first transdermal skin patch was approved by the FDA in 1979. It was a patch for the treatment of motion sickness. In the mid-1980s, the pharmaceutical companies started the development of a nicotine patch to help smokers quit smoking, and within a few months at the end of 1991 and beginning of 1992 the FDA approved four nicotine patches.

Now there are many application including weight loss.

Transdermal drug delivery (skin patch) is the non-invasive delivery of medications from the surface of the skin – the largest and most accessible organ of the human body – through its layers, to the circulatory system. Medication delivery is carried out by a patch that is attached to the body surface. Transdermal patch is a medicated adhesive pad that is designed to release the active ingredient at a constant rate over a period of several hours to days after application to the skin. It is also called skin patch. A skin patch uses a special membrane to control the rate at which the drug contained within the patch can pass through the skin and into the bloodstream.

Today drugs administered through skin patches include scopolamine (for motion sickness), estrogen (for menopause and to prevent osteoporosis after menopause), nitroglycerin (for angina), lidocaine to relieve the pain of shingles (herpes zoster). Non-medicated patches include thermal and cold patches, weight loss patches, nutrient patches, skin care patches (therapeutic and cosmetic), aroma patches, and patches that measure sunlight exposure.

Advantages and disadvantages of transdermal drug delivery

Transdermal drug delivery systems offer several important advantages over more traditional approaches, including:

* longer duration of action resulting in a reduction in dosing frequency
* Increased convenience to administer drugs which would otherwise require frequent dosing
* improved bioavailability
* more uniform plasma levels
* reduced side effects and improved therapy due to maintenance of plasma levels up to the end of the dosing interval
* flexibility of terminating the drug administration by simply removing the patch from the skin
* Improved patient compliance and comfort via non-invasive, painless and simple application

Some of the greatest disadvantages to transdermal drug delivery are:

* possibility that a local irritation at the site of application
* Erythema, itching, and local edema can be caused by the drug, the adhesive, or other excipients in the patch formulation

The main components of a transdermal patch are:

Transdermal patch may include the following components:

* Liner – Protects the patch during storage. The liner is removed prior to use.
* Drug – Drug solution in direct contact with release liner
* Adhesive – Serves to adhere the components of the patch together along with adhering the patch to the skin
* Membrane – Controls the release of the drug from the reservoir and multi-layer patches
* Backing – Protects the patch from the outer environment

Types of transdermal patches

There are four main types of transdermal patches:

Single-layer Drug-in-Adhesive

In this system the drug is included directly within the skin-contacting adhesive. In this type of patch the adhesive layer is responsible for the releasing of the drug, and serves to adhere the various layers together, along with the entire system to the skin. The adhesive layer is surrounded by a temporary liner and a backing.

Multi-layer Drug-in-Adhesive

The Multi-layer Drug-in-Adhesive is similar to the Single-layer Drug-in-Adhesive in that the drug is incorporated directly into the adhesive. The multi-layer system adds another layer of drug-in-adhesive, usually separated by a membrane. This patch also has a temporary liner-layer and a permanent backing.

Reservoir

The Reservoir transdermal system design includes a liquid compartment containing a drug solution or suspension separated from the release liner by a semi-permeable membrane and adhesive. The adhesive component of the product can either be as a continuous layer between the membrane and the release liner or as a concentric configuration around the membrane.

Matrix

The Matrix system has a drug layer of a semisolid matrix containing a drug solution or suspension, which is in direct contact with the release liner. The adhesive layer in this patch surrounds the drug layer partially overlaying it.

The future of transdermal drug delivery

Transdermal drug delivery is theoretically ideal for many injected and orally delivered drugs, but many drugs cannot pass through the skin because of skin’s low permeability. Pharmaceutical companies develop new adhesives, molecular absorption enhancers, and penetration enhancers that will enhance skin permeability and thus greatly expand the range of drugs that can be delivered transdermally.

Two of the better-known technologies that can help achieve significant skin permeation enhancement are iontophoresis and phonophoresis (sonophoresis). Iontophoresis involves passing a direct electrical current between two electrodes on the skin surface. Phonophoresis uses ultrasonic frequencies to help transfer high molecular weight drugs through the skin.

A newer and potentially more promising technology is micro needle-enhanced delivery. These systems use an array of tiny needle-like structures to open pores in the stratum corneum and facilitate drug transport. The structures are small enough that they do not reach the nerve endings, so there is no sensation of pain. These systems have been reported to greatly enhance (up to 100,000 fold) the permeation of macromolecules through skin.

Burn Fat with Slimming Patch

Find out How to Burn Fat with Slimming Patch

Herbal weight patches work by administering their particular ingredients into the bloodstream via the skin with an adhesive patch. This process is known as ‘transdermal’. Patches are not a new thing as nicotine patches and even insulin delivery patches for diabetics have been around for years.

And slimming patches are overshadowing traditional slimming pills due to it being a less risky form of losing weight for there are generally no side effects as a result of using a patch.

Herbal slimming patches work by reducing appetite, increasing metabolism and therefore burning fat and losing calories. Ingredients in slimming patches do vary, although they all aim to help the user lose weight effectively as with slimming pills a lot of the ingredients are not adequately absorbed by the body, plus there is the added benefit of using one patch a day rather than having to take several pills a day. It is also preferable to people who either struggle or dislike taking pills and eliminates any possible stomach discomfort because the ingredients do not have to be digested.

Many slimming patches contain ingredients such as Guarana, 5HTP, Flaxseed Oil and Lecithin although ingredients vary from patch to patch. In principal they work by gradually releasing the ingredients and nutrients through the skin into the bloodstream in a steady manner, while you are wearing the patch you are continuously getting a regular dose throughout the day.

Once the ingredients are in your bloodstream they head for the thyroid gland since this is what regulates your metabolism. The ingredients then boost the production of iodine that helps faster burning of fats and calories. They limit your food intake by suppressing appetite so less food will be consumed and more weight will be lost. So not only does a herbal slimming patch level out your metabolism which means quicker and more efficient fat burning but also stop you from getting food cravings, so it acts as a dual action system, helping you lose weight faster.

With so many slimming patches to choose from, there is only one patch you need to try and that is The Slim Weight Patch, rated the number one weight loss patch, it has undergone stringent medical trials and is clinically approved and it truly surpasses the rest. Convenient to use, small and discreet, it melts fat away effortlessly and easily, no side effects and it is even waterproof so you can swim whilst wearing a Slim Weight Patch.

Simply apply one patch a day to a clean hair free area of skin and discard the following day and replace with a new one, once it’s on you simply let the patch do its magic. You will absorb up to 95% of the nutrients thanks to its amazing transdermal technology, it will reach the cells precisely where it is needed for fast weight loss. To find out more information and to purchase the Slim Weight Patch visit the official website.

Herbal Weight Loss Patch

Why Herbal Weight Loss Patch Is Better than Herbal Capsules

There are many Herbal weight loss capsules available on the market to buy, all claiming that by taking these supposedly ‘safe’ supplements you will suddenly, like magic lose weight. What is unknown to many purchasers is that these capsules are not always as ‘natural’ as they seem. Even though they appear to be made of totally natural herbal, organic ingredients many actually contain harmful chemicals that have very nasty and detrimental side effects.

A lot of them are contaminated with ingredients that are not even approved by the FDA or even clinically or medically proven to work. So not only will you be wasting unnecessary money on a product that more than likely won’t help you to lose weight, you could risk doing yourself serious harm long term. And since everybody is different, one person will be able to tolerate the ingredients no problem, but the other may not and weight loss may not be the only problem they will have to deal with.

The other downside with herbal weight loss pill is that you have to remember to take them every single day and it can be easy to forget especially in today’s busy society. Many will also require quite radical changes to your diet and need a considerable amount of exercise to attain any effect on your weight whatsoever.

Merely taking herbal supplements alone might not be enough to fight the flab. Not only this, any nutrients in the herbal weight loss pills are often destroyed by the stomach and liver before reaching the bloodstream. As little as 5% of goodness is absorbed by the body when taking supplements orally. They can also be very pricey and unbeknownst to many you could literally be throwing your money away.

There is a much safer alternative to this problem. And that is the Slim Weight Patch by Roduve. It is an herbal weight loss patch, completely safe and free of any side effects whatsoever.

It is highly effective, very simple to use and will work 24/7 as you apply the patch daily, using its revolutionary transdermal technology it delivers its potent ingredients directly through the skin where it is needed for maximum absorption. It increases metabolism and ensures you are burning off the calories in a controlled and safe manner.

It is pharmaceutically developed, so you can be sure of the authenticity of the product and be sure you are using a product that really works. With no fuss, simply applying the discreet patch everyday and forgetting it is even there, knowing it is business as usual as you go on about your day while losing weight quickly and easily.

The Slim Weight Patch is great value for money and even comes complete with a 180 day money guarantee so it really is money well worth spent.