What drugs can be absorbed by skin? A guide to transdermal delivery

October 14, 2025 •

4 min read

The first transdermal patch was approved by the FDA approximately 40 years ago, revolutionizing how certain medications are delivered to the body. Today, many people wonder what drugs can be absorbed by skin for systemic delivery, avoiding the need for oral consumption.

Quick Summary

Explore how the body's largest organ, the skin, facilitates the absorption of specific drugs. This guide covers how molecules permeate the skin's barrier, common examples like hormones and pain patches, and the technology involved.

Key Points

Transdermal vs. Topical: Transdermal drugs are absorbed into the bloodstream for systemic effects, unlike topical drugs which act locally on the skin's surface.
Permeability Factors: A drug's ability to be absorbed depends on its low molecular weight, moderate oil-solubility, and the condition of the skin's outer layer, the stratum corneum.
Diverse Applications: Common transdermal medications include hormone replacements (estrogen, testosterone), pain relief (fentanyl, lidocaine), and nicotine for smoking cessation.
Controlled Release: Modern transdermal patches are engineered to provide a steady, predictable release of medication over an extended period, which improves patient compliance.
Bypasses First-Pass Metabolism: Transdermal delivery avoids the digestive system and liver, which can increase a drug's bioavailability and reduce certain side effects.
Enhanced Delivery Technology: Innovations like microneedle arrays can create temporary pathways through the stratum corneum to deliver larger or less permeable drug molecules more effectively.
Site of Application Matters: The location of a patch or cream application can influence the absorption rate due to varying skin thickness and blood flow across the body.

What is Transdermal Drug Delivery?

Transdermal drug delivery is a method of administering medication by applying it to the skin's surface, where it is then absorbed into the bloodstream for systemic effects. This differs significantly from topical application, where the goal is a localized effect on the skin itself, such as with an antibiotic cream for a rash. For a medication to be effective transdermally, it must be formulated to penetrate the skin's primary barrier, the stratum corneum, to reach the capillaries in the dermis layer below.

The Science of Skin Absorption

For drugs to cross the skin barrier, they must overcome the tightly packed, lipid-rich cellular structure of the stratum corneum. The process typically relies on passive diffusion, moving from a high concentration area (the patch or cream) to a low concentration area (the body). Drugs can pass through the skin via several pathways:

Intercellular Route: This is the most common pathway, where drugs diffuse through the lipid matrix that surrounds the skin cells. This route is favored by lipid-soluble (lipophilic) drugs.
Transcellular Route: Less common, this route involves drugs passing directly through the cells themselves, which requires them to cross the lipid bilayer of each cell membrane.
Transappendageal Route: This pathway uses hair follicles and sweat glands as potential conduits for drug absorption. While these openings account for a small fraction of the skin's total surface area, they can still provide a route for entry, especially for molecules that don't easily cross the stratum corneum.

What Drugs Can Be Absorbed by Skin?

A wide range of medications, particularly those that are potent and effective at low doses, can be delivered transdermally. Here are some of the most common examples:

Hormone Replacement Therapy and Contraception Transdermal patches provide a steady, controlled release of hormones, which can be more stable than oral alternatives.

Estrogen: Used to manage menopausal symptoms.
Testosterone: Used to treat hypogonadism in men.
Hormonal Contraceptives: Patches containing a combination of estrogen and progestin.

Pain Management Transdermal patches and gels can deliver potent analgesics directly to the bloodstream or for localized relief.

Fentanyl: A powerful opioid for chronic, severe pain.
Buprenorphine: An opioid agonist used for both chronic pain and opioid addiction treatment.
Lidocaine: Used for localized pain relief, such as for post-herpetic neuralgia.
Diclofenac: An NSAID available in patch or gel form for localized pain.

Cardiovascular Medication

Nitroglycerin: Used to prevent angina (chest pain) by relaxing blood vessels.
Clonidine: A medication for hypertension (high blood pressure).

Central Nervous System Medication

Methylphenidate (Daytrana): A stimulant patch for treating ADHD.
Rivastigmine (Exelon): Used for managing Alzheimer's and Parkinson's disease.
Rotigotine (Neupro): Used for Parkinson's disease and restless legs syndrome.
Selegiline (Emsam): A patch used for major depressive disorder.
Scopolamine (Transderm-Scop): A patch for preventing nausea and vomiting associated with motion sickness.

Lifestyle and Miscellaneous

Nicotine: Used in patches for smoking cessation therapy.

Factors Influencing Transdermal Absorption

Several factors can affect how effectively a drug is absorbed through the skin:

Drug Properties: For passive diffusion to be effective, a drug should ideally have a low molecular weight (under 500 daltons) and moderate lipophilicity (oil-solubility).
Skin Condition: The integrity of the skin's barrier is critical. Damaged, inflamed, or diseased skin can have increased permeability, potentially leading to higher absorption and risk of side effects. Skin hydration can also increase permeability.
Application Site: Different areas of the body have different skin thickness and blood flow. Thinner skin and areas with better circulation, like the upper chest or upper arm, typically show higher absorption rates compared to thicker skin areas like the back or feet.
Formulation and Enhancement Techniques: The formulation of the product (creams, gels, patches) and the use of chemical penetration enhancers can significantly impact absorption. Newer technologies like microneedle arrays can create temporary micropores to improve delivery, especially for larger molecules.

Transdermal vs. Oral Drug Delivery: A Comparison

To understand why transdermal delivery is used for some medications, comparing it to the more common oral route is helpful. PMC: Enhancing Permeation of Drug Molecules Across the Skin via Nanocarriers


Feature	Transdermal Delivery	Oral Delivery
Drug Absorption	Gradual and controlled absorption into the systemic circulation.	Fluctuating drug levels due to single dose spikes.
Bioavailability	Avoids first-pass metabolism in the liver, potentially increasing drug bioavailability.	Subject to first-pass metabolism, which can reduce drug concentration.
Side Effects	Minimized systemic side effects; avoids gastrointestinal irritation.	Potential for gastrointestinal side effects and other systemic issues.
Patient Compliance	Improved compliance with less frequent dosing (e.g., weekly patches).	Requires remembering to take multiple doses daily.
Suitable Drugs	Limited to potent, low-molecular-weight, and moderately lipophilic compounds.	Widely applicable to a large variety of drugs.
Discontinuation	Easily reversible by removing the patch.	Requires waiting for the drug to be eliminated from the system.

Conclusion

Transdermal drug delivery is a highly effective, non-invasive method for administering specific medications that benefit from a steady, controlled release into the bloodstream. By bypassing the digestive system, it can enhance bioavailability and minimize gastrointestinal side effects. However, due to the skin's natural barrier function, only a select group of medications with suitable physicochemical properties can be delivered this way. Innovations like advanced patch designs and microneedles continue to expand the potential of this delivery route, offering significant advantages for patient compliance and therapeutic consistency, particularly for long-term treatments. As with any medication, proper use and consultation with a healthcare professional are essential to ensure efficacy and safety.

Frequently Asked Questions

A topical cream is designed to act locally on the skin's surface for conditions like rashes or muscle soreness, with minimal systemic absorption. A transdermal patch, however, is formulated to deliver medication through the skin and into the bloodstream for a systemic, body-wide effect.

The skin's primary function is to serve as a protective barrier. Most drugs cannot penetrate this barrier effectively due to their molecular size or polarity. Transdermal delivery is generally limited to potent drugs with small, lipid-soluble molecules that can diffuse through the skin's outer layers.

Yes, drugs absorbed transdermally can cause systemic side effects, similar to other administration routes, although they often avoid gastrointestinal issues. Some individuals may also experience skin irritation, redness, or allergic reactions at the application site.

The onset of action for transdermal medication is typically slower than oral or intravenous routes because the drug must first penetrate the skin barrier. This delay can vary depending on the drug, formulation, and individual skin properties.

Yes, damaged or compromised skin, such as from cuts, burns, or dermatitis, can have increased permeability. This can lead to higher-than-expected absorption rates, increasing the risk of adverse effects or even overdose, especially with potent drugs.

Key advantages include a more stable and consistent drug level in the blood, improved patient compliance due to less frequent dosing, and bypassing first-pass metabolism in the liver. This can lead to increased drug bioavailability and fewer gastrointestinal side effects.

Yes, transdermal patches come in various designs, including matrix patches (drug embedded in an adhesive layer) and reservoir patches (drug in a liquid gel compartment). These designs control the rate and duration of drug release.