Chapter 3 - Basic principles of transdermal drug delivery

Abstract

The first part of this chapter discusses the principles of transdermal drug delivery. When penetrating the skin via the transcellular route, a drug molecule partitions and diffuses through keratinocytes. There are 4–20 lipid lamellae present between adjoining keratinocytes. Transdermal transport of penetrants can change as a function of skin hydration levels as well as chemical properties, permeant sizes, hydrophilicities, and diffusivities. Percutaneous drug delivery projects typically entail the experimental determination of transcutaneous flux values. This can be done in vitro using human skin or animal skin models including guinea pig, rat, or pig skin. Excised human skin is desirable for most in vitro permeation studies but because of ethics, most researchers use nonhuman skin models for preliminary experiments. Porcine skin is commonly utilized for in vitro diffusion studies because the histologic, biochemical, and permeability properties are comparable to those of the human skin. The skin is usually placed between the diffusion cells (vertical or horizontal) and a solution of the drug is put in the donor chamber. At different intervals, the drug solution is taken from the receiver chamber and assayed with either enzyme-linked immunosorbent assay, liquid chromatography-mass spectrometry, or any other suitable analytical technique. Once drug concentration is determined, the cumulative amount versus time curve is plotted and the slope of the linear portion of this curve is used to compute the flux value. For in vivo skin permeation experiments, drug delivery scientists typically use rodents such as hairless guinea pigs, hairless rats, or hairless mice due to their relatively low cost, availability, small size, and simple handling. The last portion of this chapter focuses on the physicochemical determinants of percutaneous penetration. The skin permeation of a compound depends on the molecular weight, hydrophobicity, and hydrogen bonding. Biological factors are also important as pediatric and geriatric patients require different considerations in the design, formulation, and administration of transdermal therapeutic systems.