Transdermal drug absorption is the process where medications are absorbed through the skin. This method allows therapeutic substances to enter the bloodstream directly, bypassing the digestive system. By avoiding the gastrointestinal tract, transdermal delivery circumvents “first-pass metabolism” in the liver, which can reduce a medication’s effectiveness when taken orally. This approach also enables a steady, controlled release of the drug into the body over an extended period.
How Skin Absorption Occurs
The skin, the body’s largest organ, acts as a protective shield while allowing certain substances to pass through its layers. It consists of three primary layers: the epidermis, dermis, and subcutaneous tissue. The outermost part of the epidermis, the stratum corneum, serves as the main barrier to drug penetration due to its tightly packed dead skin cells and lipid matrix.
The most common way drugs penetrate the skin is through passive diffusion. Drug molecules move from an area of higher concentration, where the medication is applied, to an area of lower concentration within the skin and bloodstream. Drugs can diffuse through the stratum corneum cells (transcellular route) or, more commonly, through the spaces between these cells (intercellular route).
Beyond the stratum corneum, some drugs can also find pathways through skin appendages like hair follicles and sweat glands. These routes, though a small percentage of the skin’s surface, provide alternative channels for drug entry, especially for molecules that struggle with the primary stratum corneum barrier. Once past the stratum corneum, drugs diffuse into the dermis, where they are absorbed by capillaries and enter the systemic circulation.
Types of Medications Absorbed Through Skin
Many medications are formulated for transdermal delivery, chosen for properties that allow them to pass through the skin barrier. These drugs typically have a small molecular weight, ideally less than 500 Daltons, and a balance of lipid and water solubility. This balance enables them to navigate both the lipid-rich stratum corneum and the more aqueous deeper skin layers. Additionally, drugs suitable for transdermal patches are often potent, requiring a low daily dose, usually less than 20 milligrams.
Pain relievers, particularly opioids like fentanyl and buprenorphine, are frequently delivered transdermally for chronic pain management. Fentanyl patches, for instance, provide continuous release over 72 hours, offering steady pain relief and avoiding frequent oral dosing. This method benefits patients needing consistent pain management or those with difficulty taking oral medications.
Hormones, such as estrogen and testosterone, are also commonly absorbed through the skin. Estrogen patches are used in hormone replacement therapy to alleviate menopausal symptoms and help prevent osteoporosis. Transdermal estrogen avoids initial liver metabolism, which can reduce certain risks associated with oral hormone therapies.
Other examples include nicotine for smoking cessation, delivered via patches to gradually reduce cravings and withdrawal symptoms. Medications for motion sickness, such as scopolamine, are also available as transdermal patches, continuously releasing the drug over several days to prevent nausea and vomiting. Nitroglycerin patches prevent angina by continuously releasing the vasodilator, helping to relax blood vessels and reduce the heart’s workload.
Factors Affecting Skin Absorption
Drug absorption through the skin is influenced by drug properties and skin characteristics. For effective penetration, drug molecules typically need to be under 500 Daltons to pass the stratum corneum barrier. Lipid solubility is also significant, as lipophilic compounds generally permeate the outer skin layers more easily than hydrophilic ones. However, a balanced solubility in both lipid and aqueous environments is often beneficial for deeper penetration into the epidermis and dermis.
The condition of the skin directly impacts drug absorption. Skin thickness varies across the body; thinner areas like the face or behind the ear allow greater absorption than thicker areas like the palms and soles. Skin hydration also affects permeability, as well-hydrated skin tends to be more permeable, while very dry or overly wet skin can hinder absorption. Damaged skin, due to cuts, burns, or certain diseases, can also lead to increased drug absorption.
Environmental and physiological factors also play a role in absorption. Higher skin temperatures can increase drug permeation by enhancing blood flow to the application site and hydrating the stratum corneum. Increased blood flow promotes removal of absorbed drugs into systemic circulation. The specific application site on the body can also influence absorption rates due to regional differences in skin characteristics and density of hair follicles and sweat glands.
Common Transdermal Delivery Methods
Transdermal drug delivery utilizes various formulations and devices to facilitate medication passage through the skin. Transdermal patches are a common method, providing controlled, sustained release over an extended period. These patches typically consist of a backing layer, a drug reservoir or matrix, a release-controlling membrane, and an adhesive layer. Some patches, known as matrix systems, have the drug dispersed within the adhesive, while reservoir systems hold the drug in a separate compartment.
Creams, gels, and ointments represent other frequently used transdermal delivery methods. These topical formulations are applied directly to the skin, allowing the drug to diffuse from the vehicle into the skin layers. Creams are typically oil-in-water emulsions, gels are semi-solid systems, and ointments are generally oil-based preparations. The specific composition of these formulations, including penetration enhancers, influences how effectively the drug is absorbed.