Transdermal Drug Delivery Systems

Transdermal Drug Delivery Systems (TDDSs)

• Facilitate the passage of therapeutic quantities of drug substances through the skin and into the general circulation for systemic effects.
• First conceived by Stoughton in 1965 and the first transdermal system, Transderm Scop (Baxter), was approved by the FDA in 1979 for prevention of nausea and vomiting associated with travel.

Percutaneous Absorption

• Evidence of percutaneous drug absorption can be found through measurable blood levels of the drug, detectable excretion of the drug and/or its metabolites in the urine, and clinical response of the patient to the therapy.
• For transdermal drug delivery, it is considered ideal for the drug to migrate through the skin to the underlying blood supply without buildup in the dermal layers.

Structure of the Skin

• The skin is composed of the stratum corneum (the outer layer), the living epidermis, and the dermis, which together provide the skin's barrier layers to penetration by external agents.
• The film that covers the stratum corneum is composed of sebum and sweat, but is not a significant factor in drug penetration.

Percutaneous Absorption Mechanism

• Percutaneous absorption of a drug generally results from direct penetration of the drug through the stratum corneum, a 10- to 15-mm-thick layer of flat, partially desiccated nonliving tissue.
• The stratum corneum is composed of approximately 40% protein (mainly keratin) and 40% water, with the balance being lipid.
• A drug's main route of penetration is through the unoccupied channels of the lipid component.
• The lipid content is concentrated in the extracellular phase of the stratum corneum and forms to a large extent the membrane surrounding the cells.

Factors Affecting Drug Absorption

• The rate of drug movement across the stratum corneum depends on its concentration in the vehicle, its aqueous solubility, and the oil-water partition coefficient between the stratum corneum and the vehicle.
• Substances with both aqueous and lipid solubility characteristics are good candidates for diffusion through the stratum corneum, epidermis, and dermis.
• Drug concentration is an important factor, and the amount of drug percutaneously absorbed per unit of surface area per time interval increases with an increase in the concentration of the drug in the TDDS.