Transdermal patch
Encyclopedia
Adhesive
An adhesive, or glue, is a mixture in a liquid or semi-liquid state that adheres or bonds items together. Adhesives may come from either natural or synthetic sources. The types of materials that can be bonded are vast but they are especially useful for bonding thin materials...
patch that is placed on the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
to deliver a specific dose
Dose (biochemistry)
A dose is a quantity of something that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement...
of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of medication delivery such as oral, topical, intravenous, intramuscular, etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier; as a result, only medications whose molecules are small enough to penetrate the skin can be delivered by this method. A wide variety of pharmaceuticals are now available in transdermal patch form.
The first commercially available prescription patch was approved by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
in December 1979. These patches administered scopolamine
Scopolamine
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
for motion sickness
Motion sickness
Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
.
Development
Before these patches go into the market, they have to be carefully studied. One way to study these patches are through the use of Franz Diffusion Cell systems. This system is used to study the effects of temperature on the permeated amount of a specific drug on a certain type of membrane, which in this case would be the membrane that is used in the patches. A Franz Diffusion Cell system is composed of a receptor and a donor cell. In many of these research studies the following procedure is used. The donor cell is set at a specific temperature (the temperature of the environment ), while the receptor cellReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
is set at different one (temperature of the body).
Different runs are performed using different temperatures to study the impact of temperature on the release of a certain medicament through a certain type of membrane. Although different concentrations of the medicament are used in this study, they do not affect the amount permeated through the membrane (the process is constant). From Chemical kinetics it’s concluded that these studies are zero order, since the concentration plays no role in the permeated amount through the membrane.
Some pharmaceuticals must be combined with substances, such as alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, within the patch to increase their ability to penetrate the skin in order to be used in a transdermal patch. Others can overwhelm the body if applied in only one place, and are often cut into sections and applied to different parts of the body to avoid this, such as nitroglycerin. Many molecules, however, such as insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, are too large to pass through the skin without it being modified in some way. Several new technologies are being investigated to allow larger molecules to be delivered transdermally.
Popular uses
- The highest selling transdermal patch in the United States is the nicotine patchNicotine patchA nicotine patch is a transdermal patch that releases nicotine into the body through the skin. It is used as an aid in nicotine replacement therapy , a process for smoking cessation. The first published study of the pharmacokinetics of a transdermal nicotine patch in humans was authored by Jed E....
, which releases nicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
in controlled doses to help with cessation of tobacco smokingTobacco smokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
. The first commercially available vapour patch to reduce smoking was approved in Europe in 2007.
- Two opioidOpioidAn opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
medications used to provide round-the-clock relief for severe pain are often prescribed in patch form: Fentanyl (marketed as DuragesicDuragesicDuragesic and Durogesic are trade names of fentanyl transdermal therapeutic systems, and are used for relief of moderate to severe pain. Since Duragesic/Durogesic release Fentanyl, a potent opioid, slowly through the skin, one patch may provide 72 hours of pain relief...
) and BuprenorphineBuprenorphineBuprenorphine is a semi-synthetic opioid that is used...
(marketed as BuTransBuprenorphineBuprenorphine is a semi-synthetic opioid that is used...
).
- Estrogen patchEstrogen patchThe estrogen patch is a delivery system for estradiol, which is used as hormone replacement therapy to treat the problems of menopause, such as hot flashes and vaginal dryness, or to prevent osteoporosis...
es are sometimes prescribed to treat menopausalMenopauseMenopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
symptoms as well as post-menopausal osteoporosisOsteoporosisOsteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. Other transdermal patches for hormone delivery include the contraceptive patchContraceptive patchA contraceptive patch is a transdermal patch applied to the skin that releases synthetic estrogen and progestin hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contraceptive pill with perfect use, and the patch may be more effective in typical use.The...
(marketed as Ortho Evra or Evra) and testosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
patches for both men (Androde) and women (Intrinsa).
- Nitroglycerin patches are sometimes prescribed for the treatment of angina in lieu of sublingual pills.
- Transdermal scopolamineScopolamineScopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
is commonly used as a treatment for motion sicknessMotion sicknessMotion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
.
- The anti-hypertensive drug ClonidineClonidineClonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
is available in transdermal patch form under the brand name Catapres-TTS.
- EmsamEmsamEmsam is the trade name of an antidepressant of the monoamine oxidase inhibitor class. Emsam is a transdermal patch containing the MAOI selegiline. Selegiline, in small doses, is most commonly used in the treatment of Parkinson's disease. It is also effective in higher doses for the treatment...
, a transdermal form of the MAOIMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
selegilineSelegilineSelegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...
, became the first transdermal delivery agent for an antidepressantAntidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
approved for use in the U.S. in March 2006.
- DaytranaDaytranaDaytrana is a medicinal patch marketed by Shire Pharmaceuticals and developed under contract by Noven Pharmaceuticals that was approved in June 2007. In the literature, Daytrana is most commonly referred to as Methylphenidate Transdermal System .Daytrana is approved by the U.S...
, the first transdermal delivery agent for the Attention Deficit Hyperactivity Disorder (ADHD) drug methylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(otherwise known as Ritalin or Concerta), was approved by the FDA in April 2006.
- Vitamin B12Vitamin B12Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
may also be administered through a transdermal patch. CyanocobalaminCyanocobalaminCyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
, a highly stable form of vitamin B12, is compatible with transdermal patching.
- RivastigmineRivastigmineRivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which...
, an Alzheimer'sAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
treatment medication, was released in patch form in 2007, under the brand name Exelon
Adverse events
- In 2005, the FDA announced that they were investigating reports of death and other serious adverse events related to narcoticNarcoticThe term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
overdose in patients using DuragesicDuragesicDuragesic and Durogesic are trade names of fentanyl transdermal therapeutic systems, and are used for relief of moderate to severe pain. Since Duragesic/Durogesic release Fentanyl, a potent opioid, slowly through the skin, one patch may provide 72 hours of pain relief...
, the fentanyl transdermal patch for pain control. The Duragesic product label was subsequently updated to add safety information in June 2005.
- In 2007, Shire and Noven Pharmaceuticals, manufacturers of the DaytranaDaytranaDaytrana is a medicinal patch marketed by Shire Pharmaceuticals and developed under contract by Noven Pharmaceuticals that was approved in June 2007. In the literature, Daytrana is most commonly referred to as Methylphenidate Transdermal System .Daytrana is approved by the U.S...
ADHD patch, announced a voluntary recall of several lots of the patch due to problems with separating the patch from its protective release liner. Since then, no further problems with either the patch or its protective packaging have been reported.
- In 2008, two manufacturers of the Fentanyl patch, ALZA Pharmaceuticals (a division of major medical manufacturer Johnson & JohnsonJohnson & JohnsonJohnson & Johnson is an American multinational pharmaceutical, medical devices and consumer packaged goods manufacturer founded in 1886. Its common stock is a component of the Dow Jones Industrial Average and the company is listed among the Fortune 500....
) and Sandoz, subsequently issued a recall of their versions of the patch due to a manufacturing defect that allowed the gel containing the medication to leak out of its pouch too quickly, which could result in overdose and death. As of March 2009, Sandoz—now manufactured by ALZA—no longer uses gel in its transdermal fentanyl patch; instead, Sandoz-branded fentanyl patches use a matrix/adhesive suspension (where the medication is blended with the adhesive instead of held in a separate pouch with a porous membrane), similar to other fentanyl patch manufacturers such as Mylan and Janssen.
- In 2009, the FDA announced a public health advisory warning of the risk of burns during MRIMagnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
scans from transdermal drug patches with metallic backings. Patients should be advised to remove any medicated patch prior to an MRI scan and replace it with a new patch after the scan is complete.
- In 2009, an article in Europace journal detailed stories of skin burns that occurred with transdermal patches that contain metal (usually as a backing material) caused by shock therapy from external as well as internal cardioverter defibrillators (ICD).
Components
The main components to a transdermal patch are:
- 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
There are five main types of transdermal patches.
Single-layer Drug-in-Adhesive
The adhesive layer of this system also contains the drug. In this type of patch the adhesive layer not only serves to adhere the various layers together, along with the entire system to the skin, but is also responsible for the releasing of the drug. The adhesive layer is surrounded by a temporary liner and a backing.Multi-layer Drug-in-Adhesive
The multi-layer drug-in adhesive patch is similar to the single-layer system in that both adhesive layers are also responsible for the releasing of the drug.One of the layers is for immediate release of the drug and other layer is for control release of drug from the reservoir. The multi-layer system is different however that it adds another layer of drug-in-adhesive, usually separated by a membrane (but not in all cases). This patch also has a temporary liner-layer and a permanent backing.Reservoir
Unlike the Single-layer and Multi-layer Drug-in-adhesive systems the reservoir transdermal system has a separate drug layer. The drug layer is a liquid compartment containing a drug solution or suspension separated by the adhesive layer. This patch is also backed by the backing layer. In this type of system the rate of release is zero order.Matrix
The Matrix system has a drug layer of a semisolid matrix containing a drug solution or suspension. The adhesive layer in this patch surrounds the drug layer partially overlaying it. Also known as a monolithic device.Vapour Patch
In this type of patch the adhesive layer not only serves to adhere the various layers together but also to release vapour. The vapour patches are new on the market and they release essential oils for up to 6 hours. The vapour patches release essential oils and are used in cases of decongestion mainly. Other vapour patches on the market are controller vapour patches that improve the quality of sleep. Vapour patches that reduce the quantity of cigarettes that one smokes in a month are also available on the market.Regulatory aspects
A transdermal patch is classified by the U.S. Food and Drug Administration as a combination product, consisting of a medical device
Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...
combined with a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
or biological product that the device is designed to deliver. Prior to sale in the United States, any transdermal patch product must apply for and receive approval from the Food and Drug Administration, demonstrating safety and efficacy for its intended use. (needs citation)
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