Transdermal Medications

Mechanism of Action

The greatest challenge for transdermal drug delivery is diffusing active substances through the barrier formed by the many layers of the skin. The outermost (and thickest) layer of the skin, the stratum corneum, contains numerous layers of keratin-heavy corneocytes. Additionally, the stratum corneum consists of 2 chemically different regions that must be accounted for when creating transdermal drugs. There is an aqueous region at the outer surface of the keratin filaments and a lipid matrix between the filaments that active medications must diffuse through to be effective.[12]

However, recent advancements have been made in the development of enhancement delivery methods for active drugs through the transdermal route. These methods are listed below.

• Microneedles: These are tiny needles that are either hollow or solid and filled with the desired drug. The microneedles pierce through the stratum corneum without causing a painful sensation. This method's advantages include painless delivery and delivering compounds with a higher molecular weight.[13][14]
• Iontophoresis: This method uses electrical driving force to drive charged particles across the stratum corneum via electrophoresis. Through this process, a persistent low-voltage current enables the diffusion of substances across the stratum corneum. An electrical current can control the drug delivery rate under the control of a preprogrammed microprocessor unit or the patient.
• Thermal poration: Applying heat to the skin creates small pores that allow the easy diffusion of molecular substances across the stratum corneum.
• Electroporation: Applying a high electrical voltage to the stratum corneum also creates small pores through which molecular substances can diffuse.
• Conventional enhancers: A chemical substance applied first to the skin to increase the stratum corneum's permeability or change the active drug's thermodynamics.
• Ultrasound: The application of sound waves to disrupt the stratum corneum and increase its permeability.[1][2][15][16]

Administration

Transdermal patches should only be placed after a proper physical examination and consideration of any associated comorbidities. The following steps are a general overview of administering a transdermal patch.

• Proper disinfecting and cleaning of skin where the patch is applied
• Application of patch in the desired area
• A follow-up appointment to ensure that the patient experiences no adverse skin reactions
• Proper adherence to the guidelines of the transdermal patch for future use

The administration of transdermal patches varies based on the drug administered.[17] However, certain steps generally apply to all transdermal patches:

• The patient should clean and disinfect the area where they will apply the patch with clear water, patting it until it is completely dry. They should avoid using any soaps, alcohols, lotions, or oils immediately before applying the patch.
• They should open the pouch containing the patch and remove it from the pouch. Then, peel off both parts of the protective liner from the back of the patch, being careful not to touch the adhesive side.
• The patient should then immediately press the adhesive side of the patch onto their skin with the palm of their hand.
• Hold or press the patch firmly for at least 30 seconds, ensuring the patch sticks well to the skin, especially at the edges.
• If the patch does not adhere well or becomes loose following application, they can use first-aid tape to tape the edges to their skin. If the patch still fails to adhere well to the skin, they can use see-through dressings but should not cover the patch with any other type of bandage or tape.
• If a patch falls off before it is time to remove it, the patient must dispose of it properly and apply a new patch, following the same dosing interval as the original patch. In such cases, it is advisable to contact their clinician's office or pharmacist.
• Following the successful application of the patch, the patient should wash their hands with water immediately.
• When it is time to change the patch, the patient peels off the old patch and applies the new patch to a different area of the skin.
• After removing the patch, the patient should fold it over with the adhesive sides together and dispose of it properly.

The patient should select different sites each time the patch is applied to avoid skin irritation. Some patches are only meant to be worn for part of a day (eg, 12 hours), while others are intended for several days. For example, fentanyl patches are worn for 72 hours and then removed and reapplied.

Patients must understand that a removed patch can still contain enough medication to cause problems if they do not dispose of it properly. This is especially concerning if children have access to discarded patches. Patches should not be used if damaged or torn, as this may cause a "dose dumping" phenomenon where the medication is dispensed more rapidly than intended. If patients have any questions about their transdermal patches, they should contact their clinician or pharmacist immediately.

Adverse Effects

The typical adverse effects caused by transdermal drug delivery include adverse cutaneous reactions. Transdermal patches are the most common delivery method for active substances, but they can irritate the skin and cause pruritis, burns, and redness in the surrounding area.[5] Additionally, allergic reactions are reported for all types of patches on the skin due to the active substance administered. The most common skin reactions include contact dermatitis and allergic contact dermatitis, usually caused by the drug or the patch, including adhesives and excipients.[18][19]

Applying multiple patches when only a single is prescribed or leaving a patch in place for longer than directed can lead to excessive drug absorption and increase the risk of overdose and toxicity.

Contraindications

Transdermal drug delivery is contraindicated for patients with the following conditions.[20]

• Allergies to the active substance contained in the transdermal patch
• Essential fatty acid deficiency
• Psoriasis
• Ichthyosis
• Atopic dermatitis
• Increased ultraviolet radiation exposure
• Premature neonate
• Pregnant women (depending on the administered drug)

Monitoring

The most significant issue associated with transdermal drug delivery is the likelihood of skin irritation caused by penetration enhancement techniques and the transdermal patch itself. In response, models have been developed to predict the likelihood of skin irritation due to drug or vessel interaction using solubility and skin irritation studies using the PII test to detect redness or swelling 24 hours after administering the patch.[12][21]

Toxicity

The toxicity of the transdermal patch depends on the active substance administered through transdermal drug delivery and whether the patient properly follows administration directions. For specific management, please refer to the individual product labeling of drug delivery systems.

Enhancing Healthcare Team Outcomes

Proper drug administration requires interprofessional effort from various healthcare professionals, including clinicians, pharmacists, nurses, and residents. Numerous drug-related problems result in medication-related harm and low-quality healthcare for patients without appropriate regulation and administration techniques. To properly deliver a drug via transdermal patches, the following steps are necessary:

• A proper physical examination and regular updating of the patient's medical history by the prescribing clinician are essential for ensuring safe and effective treatment.
• Consult with the pharmacist about the appropriate drug based on the patient symptoms and history.
• Consult with a clinician if there are any concerns about a transdermal patch.
• The patient should go to the nearest emergency department should a life-threatening condition arise.

Techniques such as face-to-face interviews enhance communication between healthcare professionals and the cohesiveness between pharmacists, primary care physicians, and surgeons in drug-related healthcare. These techniques also include reinforcement of patient counseling points to ensure proper administration and contacting the prescriber if the patient cannot perform self-administration properly. Ultimately, these techniques allow for an amplified patient-centered approach.[22][23] With interprofessional coordination and information sharing during patient care, transdermal medications can significantly benefit the appropriate patient population, resulting in improved medication adherence and better outcomes. Communication among clinicians, pharmacists, and nurses is crucial to decreasing potential adverse effects, improving disease course and quality of life, and improving patient outcomes related to transdermal medications.