Routes of drug administration

The major routes are:

• Topical: drug in a pharmacologically inactive vehicle applied to the surface of the skin
  • Largely for local effect, but also to treat underlying tissues (e.g. topical NSAIDs)
• Transdermal: for systemic effects
• Subcutanous: drug delivered by a needle under the skin, for systemic effects
• Other epithelial routes:
  • Airways
  • Conjunctival sac
  • Nasal mucosa
  • Vaginal
  • All produce a high local concentration

Structure of skin and drug absorption

'Brick and Mortar' Model of the Stratum Corneum

• Bricks = corneocytes containing keratin macrofilaments embedded in a filaggrin matrix surrounded by a cornified cell envelope

  • Corneocytes are highly crosslinked by protein 'rivets' (corneodesmosomes) which provide tensile strength

• Mortar = multiple lamellar structures of intercellular lipids (mainly ceramides, cholesterol and free fatty acids)

  • This produces a largely hydrophobic 'intracellular glue' that can also act as a reservoir for lipid-soluble drugs e.g. topical corticosteriods

  

The stratum corneum and drug diffusion

• When a drug is applied topically, drug delivery into and across the stratum corneum is through diffusion
• Transcellular route: involves crossing the skin by directly passing through both the lipid structures of the interlamellar region and moving across corneocytes, shortest diffusion distance but very high resistance
• Intercellular route: drugs pass through the small spaces between the cells of the skin, allows the movement of small, hydrophobic drugs into and through the stratum corneum
• Transappendageal routes: certain drugs are able to penetrate via hair follicles and sweat glands

Advantages of topically applied drugs

• Application is simple and non-sterile
• Potentially allows for steady state plasma concentration of drug to be achieved over a prolonged period of time
• Avoid first pass metabolism (and potental toxicity to organs)