Is the transdermal route of drug administration always systemic or can it be topical?

Transdermal Route: Systemic vs. Topical

The transdermal route is NOT always systemic—it can be either systemic or topical depending on the formulation design and intended therapeutic goal. 1

Key Distinction Between Dermal and Transdermal Delivery

The critical difference lies in the depth of drug penetration and therapeutic intent:

• Dermal (Topical) Delivery: Drug transport is limited to various skin strata (stratum corneum, viable epidermis, dermis) without reaching systemic circulation, intended for local therapeutic effects 1

• Transdermal Delivery: Drug absorption occurs through each skin layer with access to dermal microcirculation and subsequent systemic distribution 1

Five Distinct Therapeutic Goals for Skin-Applied Drugs

When drugs are applied to the skin, they can pursue fundamentally different objectives 1:

1. Surface protection only: Remain on skin surface (sunscreens, repellents, topical antifungals/antibacterials) 1

2. Appendage targeting: Treat hair follicle or gland disorders (antiperspirants, follicular infections) 1

3. Epidermal layer treatment: Target stratum corneum and viable epidermis (emollients, exfoliants, anti-inflammatories, antihistamines) 1

4. Barrier modification: Alter skin barrier function to enhance penetration of other drugs 1

5. Systemic delivery: Achieve transdermal drug delivery for systemic therapeutic effects 1

The Multistep Process of Transdermal Absorption

True transdermal (systemic) delivery requires completion of all five stages 1:

• Partition of drug from vehicle into stratum corneum
• Penetration into stratum corneum
• Diffusion from stratum corneum into viable epidermis
• Partition from viable epidermis to dermis
• Access to systemic circulation 1

If the drug stops at any earlier stage, it remains topical rather than systemic.

Clinical Examples of Systemic Transdermal Products

Well-established transdermal systems designed specifically for systemic effects include 1:

• Hormonal therapy: Estradiol patches 1
• Pain management: Fentanyl patches 1
• Smoking cessation: Nicotine patches 1

These formulations are engineered to bypass hepatic first-pass metabolism and achieve sustained systemic drug levels 2, 3.

Common Pitfall to Avoid

Do not assume all skin-applied medications are systemic. The vast majority of topical formulations (creams, ointments, lotions) are designed for local effects only and do not achieve clinically significant systemic absorption 1. The term "transdermal" should be reserved specifically for formulations engineered to penetrate through all skin layers and reach systemic circulation 1.

The stratum corneum functions as an effective barrier that prevents most substances from achieving systemic penetration, which is why specialized transdermal delivery systems or penetration enhancers are required for systemic effects 1, 4.