Transdermal administration solves specific problems that limit medication effectiveness and patient adherence. Understanding why this route exists means seeing where traditional delivery methods break down in practice.
Some medications can’t reach patients through conventional routes. The liver destroys them before a therapeutic effect occurs. Gastrointestinal side effects force discontinuation. Injection requirements create barriers patients won’t cross. When pills and needles fail, skin delivery often provides the only path to treatment.
The Problem With Pills and Injections
Oral delivery fails for certain medications in ways that can’t be engineered around.
First-pass metabolism presents an insurmountable barrier for some compounds. The liver metabolizes more than half of certain drugs before they reach circulation. Raising the oral dose seems like a simple fix until side effects emerge or production costs make the product unmarketable. For some compounds, no safe oral dose can overcome hepatic metabolism.
Gastrointestinal damage creates a separate problem. Concentrated drugs in the stomach lining cause irritation that worsens with continued use. Systemic delivery works fine; getting the drug there causes the harm.
Oral medications also create a timing problem for therapies that need steady blood levels. Each oral dose produces a concentration spike, then drug blood levels fall over the next several hours. Hormone therapies lose effectiveness during these troughs. Pain breaks through. Cardiovascular protection weakens. The concentration cycling itself undermines treatment goals.
Injections avoid hepatic metabolism but create different barriers. Many patients won’t maintain injection schedules. Pain is one factor. So is the inability to self-administer or access to trained personnel for administration. Therapeutic efficacy doesn’t matter if adherence fails.
Why Skin Works as a Delivery Route
Skin keeps foreign substances out, but it’s not an absolute barrier.
The stratum corneum blocks most molecules while allowing specific compounds to pass. Drug molecules with molecular weights below 500 Daltons and a balance of lipophilic and hydrophilic properties can navigate intercellular or intracellular pathways, though this represents a small subset of pharmaceutical compounds.
Transdermal patches leverage this selective permeability by maintaining a high concentration at the skin surface. The concentration gradient drives controlled penetration over hours or days.
READ MORE: Transdermal Patches 101: What They Are, How They Work & Why Patients Like Them
This approach is valuable because drugs enter capillaries beneath the skin and reach systemic circulation without first passing through the liver. For compounds that are metabolized by hepatic enzymes, this bypass determines whether the drug can work at all.
Delivery kinetics also change. Patches release the drug at a controlled rate rather than producing the spikes and troughs that oral dosing creates. Blood levels hold steadier throughout the patch wear period, which matters for therapies where consistency drives outcomes.
What Makes Transdermal Delivery Possible
Not every drug works through the skin. The barrier function imposes real molecular constraints.
Molecular weight limits drug candidates. Proteins and large molecules can’t penetrate. Chemical properties matter too; compounds need the right balance of fat and water solubility to move through both lipid-rich and aqueous skin layers. Most drugs don’t meet these criteria.
Low dose requirements help. When only 10% to 30% of the applied drug reaches circulation, compounds requiring 500mg daily doses become impractical. Drugs effective at 5mg daily can work through a patch.
Sophisticated adhesive systems do more than hold patches in place. The polymer matrix stores the drug and controls release through its chemical structure. Sealing the patch against the skin traps moisture, which hydrates the stratum corneum and disrupts its lipid organization, creating better conditions for drug penetration. This is why adhesive coatings represent a critical component of effective transdermal delivery rather than just an attachment mechanism.
These constraints explain why only about 20 drugs have received FDA approval for transdermal delivery over the past four decades. Most compounds lack the necessary molecular profile.
When Skin Delivery Becomes Essential
For Drugs That Fail Other Routes
Some compounds show therapeutic promise but can’t survive the path to systemic circulation. Hepatic metabolism degrades them too quickly, or they damage the GI tract at concentrations needed for absorption. Transdermal formulation may be the only commercially viable route.
Nitroglycerin illustrates this clearly. Oral administration results in nearly complete hepatic metabolism before the drug reaches cardiac tissue. Sublingual tablets work briefly but can’t sustain the effect. Patches maintain therapeutic levels throughout the day, preventing angina episodes rather than just treating them after onset.
For Patients Who Can’t Use Standard Options
Patient factors can make conventional delivery routes impractical regardless of the drug involved.
Swallowing becomes difficult in elderly populations or during cancer treatment, when nausea also prevents reliable absorption. Complex medication schedules (taking different drugs at different times) exceed the cognitive capacity of some patients, leading to missed doses that undermine therapy.
A patch worn for several days or a week removes this complexity. One application replaces multiple daily doses. Caregivers can confirm treatment with a visual check rather than relying on patient recall. This is one reason patient education about transdermal patches matters for treatment success.
For Therapies Requiring Steady Levels
Some treatments only succeed when blood concentrations stay within a narrow range. Hormone replacement therapies lose effectiveness when levels swing. Pain control fails during concentration troughs. Cardiovascular drugs need consistent levels to maintain protection.
The evenness matters as much as the dose. Fluctuating hormones can trigger the symptoms that treatment aims to prevent. Pain medication that varies between too low and too high creates periods of both suffering and side effects. Clinical Research published in Pharmaceutical Research (2024) demonstrates that maintaining steady-state plasma concentrations through transdermal systems significantly improves therapeutic outcomes for chronic conditions compared to oral dosing.
READ MORE: 6 Advanced Adhesive Technologies That Are Transforming Modern Drug Delivery Systems
Recent Advances in Skin Delivery
Transdermal delivery fills specific gaps where pills and injections consistently fail. In most cases, transdermal cannot replace oral medications as the primary delivery method; most drugs don’t meet the molecular requirements or don’t need an alternative route.
Recent advances in permeation enhancement technologies keep expanding what’s possible. Microneedles create temporary channels through the stratum corneum. Chemical enhancers temporarily alter lipid organization. These innovations make transdermal delivery viable for drugs that molecular properties would otherwise exclude. Studies from AAPS PharmSciTech in 2024 highlight how novel penetration enhancement strategies are broadening the range of molecules suitable for transdermal administration.
Physicians gain tools for situations where standard drug administration routes prove inadequate. Patients get alternatives when pills cause intolerable problems or injections create insurmountable barriers. Pharmaceutical developers with specialized product development capabilities and rigorous quality management standards can make previously unviable compounds commercially feasible through proper process development and analytical testing.
Conclusion
When pills and injections create barriers that prevent drugs from reaching patients, transdermal delivery offers an alternative path. But the route comes with real constraints: molecular weight limits, chemical property requirements, and dose restrictions that eliminate most compounds.
Recognizing when those constraints align with compound properties helps pharmaceutical teams determine whether a transdermal formulation offers the most viable development path. Success requires expertise in polymer chemistry, formulation design, and manufacturing processes that differ from conventional drug product production.
With over 60 years of experience in patch drug delivery systems, ARx works with pharmaceutical teams to transform compounds that struggle through traditional routes into therapies that reach patients.
ARx is a patient-friendly, novel drug delivery partner. We specialize in oral thin film, buccal film, topical and transdermal patch strategies, all backed by tailored, full-scale development services. Contact us today to find the right delivery system for your API.
