Practical Considerations for Optimal Transdermal Drug Delivery

Cheryl Durand; Abdullah Alhammad; Kristine C. Willett


Am J Health Syst Pharm. 2012;69(2):116-124. 

In This Article

How TDDs Products Work

The stratum corneum, the outermost layer of the skin, is considered to be the main penetration barrier (absorption barrier) in transdermal drug delivery; it is approximately 10–20 μm thick in most parts of the body and consists of multiple layers of dead corneocytes embedded in lipid bilayers.[9] Diffusion through the stratum corneum is the rate-limiting step for the transport of drug molecules by the transdermal route.[6]

Factors that control the rate and extent of medication absorption from a TDDS include the size and lipophilicity of the molecule, the site(s) of application, the skin thickness, the drug concentration within the TDDS, the surface area covered by the patch, and the hydration status of the skin.[1,2,8] Drug entities of low molecular weight (≤500 daltons) can easily diffuse through the stratum corneum. High lipophilicity and the ability to produce desired effects at small doses are among the factors that make drugs good candidates for transdermal delivery. Effectiveness at small doses is an especially important factor, as only a limited amount of medication may be delivered by a TDDS because the size of the patch limits the amount of medication it can contain.[1,10]

In general, transdermal patches are composed of several layers, including an impermeable backing (the layer visible when the patch is applied to a patient's skin), a drug layer that contains the active ingredients and excipients, a rate-controlling membrane that controls the rate of drug availability, a contact adhesive layer that provides adhesion to the skin, and a protective cover (peel strip) to be removed before the application of the patch to the skin.[1,10]

Currently marketed TDDS products can be generally classified as reservoir or matrix systems. In a reservoir system, the drug is contained in a reservoir enclosed between the backing and rate-controlling membrane; microreservoir systems have several small reservoirs of medication rather than one large reservoir. In a matrix system, the drug is either dispersed within the adhesive itself (a drug-in-adhesive matrix) or dispersed within a matrix that lies between the backing and a separate adhesive layer.[1,6,8]

Research to develop physical or chemical methods of transdermal drug delivery that enhance skin penetration by medications is ongoing. Physical methods under investigation include iontophoresis (transferring the drug by applying an electric current), electroporation (disrupting the lipid-bilayer membrane through short, intense electric pulses), sonophoresis (using a low-frequency ultrasound technique to expedite drug transfer), and microneedles (perforating the stratum corneum with very short needles).[7] Potential chemical methods of improving the penetration of medications through the skin include the use of a prodrug, the use of an optimal salt form (to increase permeability) or ion pairs (pairing charged drugs with oppositely charged species to neutralize the charge, which enhances permeability), and molecular absorption enhancement (using chemical molecules that reduce barrier resistance).[1,2,6]

For this article, information on about three dozen currently available TDDS products commonly encountered in clinical practice was compiled through a literature search and a review of product package inserts. Additional information was obtained through direct contact with product manufacturers, particularly with regard to issues and questions generally not addressed in TDDS product packaging. Some pharmaceutical company representatives declined to divulge their surname or provide the requested information in written form.


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