Transdermal Delivery

Question 1

What is the area of the skin?

Answer 1

2m^2

Question 2

How much blood does skin receive?

Answer 2

1/3 of total blood circulation

Question 3

What is the function of the skin?

Answer 3

-barrier: protection of internal organs and fluid
-permeable: controls water loss and temp control
-sensory: pain, temp, pressure

Question 4

What are the three layers of the skin?

Answer 4

Epidermis, dermis and subcutis

Question 5

What is the main skin barrier and what % water content does it have?

Answer 5

Stratum Corneum- 40%

Question 6

How many hair follicles and sweat ducts per cm squared ?

Answer 6

40-70 follicles and 200-250 ducts per cm squared (0.1% total surface)

Question 7

What are the two classes of routes through the skin?

Answer 7

Transepidermal- through stratum Corneum via intercellular or transcelluar paths
Transapendigeal- via follicles and sweat glands (insignificant as only make up 0.1% total surface)

Question 8

What is the make up of the stratum corneum?

Answer 8

Corneocytes surrounded by intercellular neutral lipids such as ceramides (stabilises hydrophilicity) , cholesterol, free fatty acids

Question 9

Which area of lipid bilayer has enhanced drug transport and why?

Answer 9

Bimolecular leaflet- can disorder structure and fluidity

Question 10

Why characteristics do drugs need for transdermal delivery?

Answer 10

Low MW <600Da
Soluble in both oil and water
High vehicle partition coefficient (SC) ie more soluble in lipids than vehicle so doesn’t become trapped
Low MP
Needs to be potent (10-20mg max)- diluted in body

Question 11

What is the equation for percutaneous absorption (resistance model)?

Answer 11

R= h/FxDxK or for SC R=h/Fsc x Dsc x Ksc

R=magnitude of resistance by barrier
H=thickness of membrane
F=Fractional area of route
D=drug diffusion coefficient
K= tissue capacity

Question 12

What are the 4 resistances?

Answer 12

R1= vehicle resistance
R2=appendageal resistance
R3=SC resistance
R4= viable tissue resistance (epidermis)

Question 13

What is the formulation strategy equation?

Answer 13

J= (D.K/h) 🔼C. Or J= P(🔼C)

J= amount of drug penetrating
D=drug diffusion coefficient
K=partition coefficient between vehicle and SC
🔼C= drug concentration gradient across barrier
P=permeability coefficient (inverse to resistance)

Question 14

How and why would we increase D in formulation?

Answer 14

D=drug diffusion coefficient
Want to increase diffusion
Via making more lipophilic (prodrug) or
Penetration enhancers

Question 15

How and why would we increase K in formulation?

Answer 15

K=partition coefficient between sc and vehicle
Want it larger by increasing lipophilicity of drug using a polar/aqueous vehicle (no lipid competition)

Question 16

How and why would we increase 🔼C in formulation?

Answer 16

Want to increase diffusion gradient
By using drug reservoir in vehicle and ensuring saturated solution in diffusion layer

Question 17

What factors affect percutaneous absorption?

Answer 17

Skin- health,hydration,skin age (thinning), skin temp (^ = ^ absorption)
Drug-drug concentration, partition coefficient, degree of ionisation (all altered via vehicle), solubility

Question 18

What layers make up the patch?

Answer 18

Bottom- release liner
Middle- drug in adhesive
Top- backing layer

If want controlled release- rate controlling layer (nicotine)

Question 19

What are 3 examples of drug modification for transdermal drugs?

Answer 19

Prodrug-enhanced lipophilicity by covalently linking drug with inactive moiety
Ion pairs-add oppositely charged species to charged drug to make unionised
Eutectic mixture- add another component that doesn’t interact with drug allowing inhibition of crystallisation of one another- lowers MP= higher solubility

Question 20

What is an example of SC modification?

Answer 20

Penetration enhancers- DMSO- fluidises lipid bilayer (causes skin irritation and bad breath)
Lipid fluidity enhancers- DMSO- fluidises lipid bilayer

Question 21

What are examples of electrical enhancement?

Answer 21

Iontophoresis- addition of electrical current- electro migration ( charged mols) or electroosmosis (polar or neutral). Drug travels through body to get to +ve electrode
Electroporation- high voltage pulses- induces aqueous pore in lipid bilayer
Sonophoresis- ultrasound (sound waves)- creates pores

Question 22

What are examples of ways to bypass SC?

Answer 22

Jet injection- jet pierces skin, compressed air or spring
Thermal ablation-short term vaporisation of sc
Laser ablation- laser holes in skin