Transdermal delivery

Question 1

What is transdermal drug delivery (TDD)?

Answer 1

Delivery of drugs to the systemic circulation through the skin

Question 2

What are the advantages of transdermal drug delivery over other administration routes?

Answer 2

Avoidance of GIT (enzymes, pH, food)

Avoidance of first-pass metabolism

Controlled rate of drug delivery (steady state)

Reduced frequency of dosing (sustained released over 0.5 to 7 days)

Reduced inter and intra-patient variability

Drug input readily terminated

Question 3

Why is there only a limited number of drugs that can be efficiently administered by TTD?

Answer 3

Skin is an effective barrier

Few drugs are suitable for TDD

Question 4

Fill in the gaps

Answer 4

Question 5

Discuss why the stratum corneum is the main barrier for drug absorption

Answer 5

10-15 layers of corneocytes

Tightly compacted cell layers

Polygonal, elongated, flat cells

Cells contain almost only keratin

Embedded in lipid layers

Brick + mortar model

Question 6

What are the different permeation pathways through stratum corneum?

Answer 6

Transappendageal (shunt route)

• Hair follicles, sweat ducts offer pores to the dermis
• Negligible (only 0.1% of skin surface) except for ions, macromolecules

Transcellular

• Polar route for hydrophilic molecules
• Unfavourable (drugs need to partition into lipid bilayers between the cells)

Intercellular

• Apolar route for hydrophobic molecules
• Favourable (continuous pathway)

Question 7

Identify the factors that affect drug diffusion across the skin

Answer 7

Skin condition (age, body site, hydration, pathological disorders)

Physico-chemical properties of drug

• Molecular weight
• Partition coefficient between vehicle and skin
• pKa
• Solubility in vehicle
• Concentration

Question 8

Discuss Fick’s law of diffusion

Answer 8

Diffusion across the skin is passive

Depends on

• concentration gradient
• diffusivity

Question 9

Identify the main components of skin patches and draw a schematic for the three main designs

i. drug in adhesive
ii. drug in matrix
iii. drug in reservoir.

Answer 9

The main components to a transdermal patch are:

• Release Liner - Protects the patch during storage. The liner is removed prior to use.
  
  • must be peeled off before applying on the skin
• Drug - Drug solution in direct contact with release liner
• Pressure sensitive Adhesive - Serves to adhere the components of the patch together along with adhering the patch to the skin
  
  • must stick to the skin
  • must be non-irritating
• Membrane - Controls the release of the drug from the reservoir and multi-layer patches
• Backing layer - Protects the patch from the outer environment
  
  • must be occlusive
  • must be flexible

Question 10

Understand potential drawbacks of transdermal patches

Answer 10

Skin allergy/irritancy/pigmentation changes → patients advised to alternate sites of application

Can’t usually be cut → no dose adjustment

Fragile (alterations compromise drug release)

Still contain drug after use → safe disposal

Drug release rate increased with temperature (fever, sport, warm clothes) → risk of overdose

Variability in designs, administration frequency, administration site → patients, caregivers might get confused

Question 11

How to select a good drug candidate for TDD?

Answer 11

Suitable physicochemical properties

• MW: 300-500 Da
• Log P = 1-3.5
• Solubility > 100 microgram/ml
• Neutral at skin pH (5)

Potent

• Flux of a good permeant is 1 mg/cm²/day
• Patch surface area of 10cm²
• Realistic dose delivered 10 mg/day

Irritancy (to skin)

Tolerance if constant

Question 12

How do we estimate drug flux across the skin>

Answer 12

Mathematical models e.g. Potts guy

In vitro permeation studies