Transdermal drug delivery

Question 1

Advantages of transdermal drug delivery

Answer 1

Avoidance of first-pass metabolism
Drug levels in systemic circulation maintained within therapeutic window
Frequency of dosing reduced
Improved patient compliance
Drug delivery terminated by removal of patch

Question 2

Disadvantages of transdermal drug delivery

Answer 2

Skin is a tough barrier to get past
May cause irritation or sensitisation
Tolerance inducing drugs

Question 3

Skin structure

Answer 3

1. Epidermis
   Primary function is protection
   Contains keratinised squamous stratified epithelium
   10-25% water content
2. Dermis
   20-40% of total water content
   Thicker than epidermis
   Contains connective tissue (support structures, blood capillaries and lymphatic duct)
3. Hypodermis
   Contains appendages (eccrine and apocrine sweat glands, pilosebaceous duct)

Question 4

Keratinised squamous stratified epithelium

Answer 4

Stratified – many layers
Keratinised – Outermost cells are dead and have no nuclei
As cells rise to the surface, they become more flattened, compacted and dead, dense and increasingly hydrophobic

Question 5

Glands

Answer 5

1.	Eccrine sweat glands
Temperature regulation
Largely watery secretion
2.	Apocrine sweat glands
In axilla, genital regions and breasts
* Sweat is odourless but its metabolism by bacteria generates odour
3.	Sebaceous glands
Associated with hair follicle
Produce sebum from cell disintegration forming an oily protective layer of the skin

Question 6

Stratum corneum

Answer 6

The main barrier
Stops most of exogenous material
Dense, lacks of water and it is lipophilic

Question 7

Transcellular route

Answer 7

Partition in and out of the lipid and keratin domains

May form a depot or reservoir i.e. clotrimazole, sun screen

Question 8

Intercellular route

Answer 8

Through the lipid domains only
Small gaps between corneocytes (0.1 mcm wide)
Main route for small molecules i.e. nicotine

Question 9

Transappendageal route

Answer 9

Drug passage highly unlikely
Opposing flow from the gland
Best for iontophoresis, ionised molecules, steroids, areas with larger concentration of sweat glands

Question 10

Dominant properties for permeability

Answer 10

-	Lipophilicity (doesn’t reach circulation)
Impacts K
Key feature of drug acceptance
-	Molecular size
MW < 350Da
-	Adequate solubility
-	Balanced partition coefficient
-	Low melting point

Question 11

Intermediate drugs

Answer 11

• Drugs that exhibit both lipid and aqueos properties reach circulation
• If drug is too lipophilic, it will stay in stratum corneum and not diffuse into the rest of the skin
• If drug is too hydrophilic, it will not get through stratum corneum barrier