Pharmacology

Question 1

What are the three major routes of drug administration in the skin?
Which are used for systemic affects?

Answer 1

1. Topical – largely for local effect, but also to treat underlying tissues, e.g. anti-inflammatories such as Diclodfenac
2. Transdermal
3. Subcutaneous/
   depot
   Transdermal and subcutaneous - looking for drug to cross skin and enter capillary or lymphatic system and have a systemic effect which is prolonged

Question 2

What is the single most important barrier to drug penetration in the skin?
How is this overcome?

Answer 2

Stratum corneum
Brick and mortar system – mortar is lipid which surrounds the corneocyte bricks – drug diffuses through the corneocytes or follow the route of mortar

Question 3

Is the transcellular or intercellular route more commonly used?

Answer 3

Largely via the intercellular route and normally allows only diffusion of small, hydrophobic, drugs

Question 4

What is the role of the vehicle?

What are the two important factors?

Answer 4

The vehicle can profoundly influence the rate and extent of absorption of a topically applied drug
Important factors are:
1. Solubility of the drug in vehicle (Cv)
2. Maximizing the movement (or partitioning) of the drug from vehicle to the stratum corneum (Km) – the drug must ‘escape’ from the vehicle and enter the outmost layer of the stratum corneum

Question 5

What is Km?

Answer 5

Km is described as: the equilibrium solubility of the drug in the stratum corneum (sc) relative to its solubility in the vehicle (Km = Csc/Cv)

Question 6

Why are topically applied drugs poorly absorbed?

How can this be improved?

Answer 6

Topically applied drugs are generally poorly absorbed because only a small fraction partitions into the stratum corneum

• Hydration of the skin by occlusion (prevention of water loss) e.g. ointment vs cream, clingfilm
• Excipients - increase solubility of hydrophobic drugs