Transdermal Delivery Flashcards
What is the area of the skin?
2m^2
How much blood does skin receive?
1/3 of total blood circulation
What is the function of the skin?
-barrier: protection of internal organs and fluid
-permeable: controls water loss and temp control
-sensory: pain, temp, pressure
What are the three layers of the skin?
Epidermis, dermis and subcutis
What is the main skin barrier and what % water content does it have?
Stratum Corneum- 40%
How many hair follicles and sweat ducts per cm squared ?
40-70 follicles and 200-250 ducts per cm squared (0.1% total surface)
What are the two classes of routes through the skin?
Transepidermal- through stratum Corneum via intercellular or transcelluar paths
Transapendigeal- via follicles and sweat glands (insignificant as only make up 0.1% total surface)
What is the make up of the stratum corneum?
Corneocytes surrounded by intercellular neutral lipids such as ceramides (stabilises hydrophilicity) , cholesterol, free fatty acids
Which area of lipid bilayer has enhanced drug transport and why?
Bimolecular leaflet- can disorder structure and fluidity
Why characteristics do drugs need for transdermal delivery?
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
What is the equation for percutaneous absorption (resistance model)?
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
What are the 4 resistances?
R1= vehicle resistance
R2=appendageal resistance
R3=SC resistance
R4= viable tissue resistance (epidermis)
What is the formulation strategy equation?
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)
How and why would we increase D in formulation?
D=drug diffusion coefficient
Want to increase diffusion
Via making more lipophilic (prodrug) or
Penetration enhancers
How and why would we increase K in formulation?
K=partition coefficient between sc and vehicle
Want it larger by increasing lipophilicity of drug using a polar/aqueous vehicle (no lipid competition)
How and why would we increase 🔼C in formulation?
Want to increase diffusion gradient
By using drug reservoir in vehicle and ensuring saturated solution in diffusion layer
What factors affect percutaneous absorption?
Skin- health,hydration,skin age (thinning), skin temp (^ = ^ absorption)
Drug-drug concentration, partition coefficient, degree of ionisation (all altered via vehicle), solubility
What layers make up the patch?
Bottom- release liner
Middle- drug in adhesive
Top- backing layer
If want controlled release- rate controlling layer (nicotine)
What are 3 examples of drug modification for transdermal drugs?
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
What is an example of SC modification?
Penetration enhancers- DMSO- fluidises lipid bilayer (causes skin irritation and bad breath)
Lipid fluidity enhancers- DMSO- fluidises lipid bilayer
What are examples of electrical enhancement?
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
What are examples of ways to bypass SC?
Jet injection- jet pierces skin, compressed air or spring
Thermal ablation-short term vaporisation of sc
Laser ablation- laser holes in skin
