transdermal patch transdermal patch a transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. an advantage of a transdermal drug delivery route over other types of medication delivery (such as oral, topical, intravenous, or intramuscular) 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. the first commercially available prescription patch was approved by the u.s. food and drug administration in december 1979. these patches administered scopolamine for motion sickness. not to be confused with dermal patch. a 21mg dose nicoderm cq patch applied to the left arm contraceptive patch clonidine tablets and transdermal patch a transdermal patch which delivers medication is applied to the skin in a medical setting. the patch is labelled with the time and date of administration as well as the administrator's initials. microneedle patch size comparison in order to overcome restriction from the skin, researchers have developed microneedle transdermal patches (mnps), which consist of an array of microneedles, which allows a more versatile range of compounds or molecules to be passed through the skin without having to micronize the medication beforehand. mnps offer the advantage of controlled release of medication and simple application without medical professional assistance required. with advanced mnps technology, drug delivery can be specified for local usage, for example skin whitener mnps that are applied to the face. many types of mnps have been developed to penetrate tissues other than skin, such as internal tissues of the mouth and digestive tract. these promote faster and more direct delivery of the molecule to the targeted area. applications the highest selling transdermal patch in the united states of america is the nicotine patch, which releases nicotine in controlled doses to help with cessation of tobacco smoking. the first commercially available vapour patch to reduce smoking was approved in europe in 2007. two opioid medications used to provide round-the-clock relief for severe pain are often prescribed in patch form, fentanyl cii (marketed as duragesic) and buprenorphine ciii (marketed as butrans). hormonal patches: estrogen patches are sometimes prescribed to treat menopausal symptoms (as well as post-menopausal osteoporosis) and to transgender women as a type of hormone replacement therapy. contraceptive patches (marketed as ortho evra or evra) and testosterone ciii patches for both men (androderm) and women (intrinsa). nitroglycerin patches are sometimes prescribed for the treatment of angina in lieu of sublingual pills. transdermal scopolamine is commonly used as a treatment for motion sickness. the anti-hypertensive drug clonidine is available in transdermal patch form. emsam, a transdermal form of the maoi selegiline, became the first transdermal delivery agent for an antidepressant approved for use in the u.s. in march 2006. daytrana, the first methylphenidate transdermal delivery system for the treatment of attention deficit hyperactivity disorder (adhd), was approved by the fda in april 2006. secuado, a transdermal form of the atypical antipsychotic asenapine, was approved by the fda in october 2019. vitamin b12 may also be administered through a transdermal patch. cyanocobalamin, a highly stable form of vitamin b12, is compatible with transdermal patching. 5-hydroxytryptophan (5-htp) can also be administered through a transdermal patch, which was launched in the united kingdom in early 2014. rivastigmine, an alzheimer's treatment medication, was released in patch form in 2007 under the brand name exelon. in december 2019, robert s. langer and his team developed and patented a technique whereby transdermal patches could be used to label people with invisible ink in order to store medical information subcutaneously. this was presented as a boon to "developing nations" where lack of infrastructure means an absence of medical records. the technology uses a "quantum dot dye that is delivered along with a vaccine". caffeine patches, designed to deliver caffeine to the body through the skin. adverse events in 2005, the fda announced that they were investigating reports of death and other serious adverse events related to narcotic overdose in patients using duragesic, 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 daytrana 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 & johnson) 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 mri 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 permeation enhancer - these are permeation promoters for drugs, which increase delivery of drug. matrix filler - provides bulk to the matrix, and some act as matrix stiffening agents. other components include stabilizers (antioxidants), preservatives etc. types sample transdermal patches. on left is a 'reservoir' type, on the right a 'single-layer drug-in-adhesive' version. both contain exactly the same active ingredient with identical release rates. 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. it is characterized by the inclusion of the drug directly within the skin-contacting adhesive placed onto the epidermis. multi-layer drug-in-adhesive the multi-layer drug-in-adhesive patch is similar to the single-layer system; the multi-layer system is different, however, in that it adds another layer of drug-in-adhesive, usually separated by a membrane (but not in all cases). one of the layers is for immediate release of the drug, and the other layer is for controlled release of the drug from the reservoir. this patch also has a temporary liner-layer and a permanent backing. the drug release from this depends on membrane permeability and diffusion of drug molecules. 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. the drug reservoir is totally encapsulated in a shallow compartment molded from a drug-impermeable metallic plastic laminate, with a rate-controlling membrane made of a polymer like vinyl acetate on one surface. 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 a vapour patch, the adhesive layer not only serves to adhere the various layers together but also to release vapour. vapour patches release essential oils for up to 6 hours and are mainly used for decongestion. other vapour patches on the market improve quality of sleep or aid in smoking cessation. microneedle patch further information: microneedle drug delivery the microneedle patch (mnps) is a type of transdermal patch that retains the advantages, but reduces the disadvantages, of basic transdermal patches. embedding as many as 102-104 needles per square centimeter of patch, encapsulated or coated with intended drug, mnps can easily pass skin tissue known as the stratum corneum that is roughly 20 μm in thickness, allowing up to the size macromolecule to pass. the development of mnps is mainly because selective transdermal patch can deliver smaller size or micronized molecules such as nicotine and birth control that easily diffuse and penetrate the skin, but lack in delivering macro or large size molecules. the 100-1000 μm needles spread across the patch, making sure patients will not feel any discomfort from the patch. there are two types of needles used in mnps, the first one is non-water-soluble needles made out of metal, ceramic, or polymer, and the second one is water-soluble needles made out of saccharides or soluble polymers. other than skin patches, mnps can also be engineered to deliver molecules in different tissues. some that are under development include internal surfaces such as the mouth, vagina, gastrointestinal tract, and vascular wall; and external surfaces such as the skin, eyes, fingernails, anus, and scalp. this allows targeting a more specific area of wanted delivery, without having to solely rely on diffusion on blood flow like a normal transdermal patch. mnps drug delivery as mentioned earlier, mnps deliver more efficient delivery compared to topical or oral intake. in drug delivery study, researchers want to gain faster peak concentrations (cmax) in mnps compared to other methods. study shows that mnps reach peak concentration as fast as 20 minutes (tmax), while oral intake reaches peak concentration in one hour. furthermore, the cmax from mnps is higher up to six times, compared to oral intake. making the delivery fast and the body gets the most concentration of intended drugs. this value is only matched with direct injection, but with skin trauma and people with needle phobia, mnps might be an alternative to reach roughly the same time and concentration. in order to get more direct local delivery, mnps can be used in different tissues other than the skin. in table 1, there are at least five internal surfaces that mnps have been studied for its delivery and four other external surfaces other than the skin. mnps may puncture stratum corneum to deliver directly to the dermis layer. table 1: tissues studied for mnps delivery internal surface external surface mouth skin vagina eye gastrointestinal tract fingernail vascular wall anus scalp types of microneedle there are many types of microneedle that are distinguished by the shape and other characteristics. the types include: dissolvable mnps, solid non-soluble mnps, and hollow mnps. different mnps may be chosen depending on the situation and the drug properties. soluble or dissolvable mnps one of the types of mnps are water-soluble needles made out of soluble polymers or saccharide. however, dissolvable needles cannot efficiently deliver drugs to the dermal layer. drug maximum concentration cannot be carried out to the skin, as the needles will dissolve beforehand. fortunately, researchers have developed a water-insoluble backing layer, making the needle last longer in the human body environment. this design enables efficient delivery of more than 90% of the drug within 5 minutes of application of mnps to the skin. non-soluble or undissolvable