Module 2B transdermal drug delivery systems

Question 0

What are the essential factors affecting per cutaneous absorption in transdermal drug delivery (10)

Answer 0

Not all drug substances are suitable for transdermal delivery:
1. The physical and chemical properties of the drug
2. Nature of the carrier vehicle
3. Condition of the skin
4. Drug concentration
5. Size of the area do application (the larger the more drug absorbed)
6. Hydration of the skin
7. The drug should have a greater attraction to the skin than the
vehicle
8. Ideal molecular weight (believed to be <400)
9. Absorption appears better when applied to a thin horny layer
10. Time left in contact with skin (the longer the more drug absorption

Question 1

What are the major potential routes of drug entry into viable tissue of the skin? (3)

Answer 1

1. Via the sweat ducts
2. Across the continuous stratum corneum
3. Through the hair follicles with their associated sebaceous glands

Question 2

List examples to illustrate the research efforts attempted to maximise the bioavailability of drugs applied to the skin (14)

Answer 2

Most drugs penetrate the skin poorly and many research efforts have been attempted to maximise the input of such drugs
1. Drug or prodrug selection
2. Chemical potential adjustment
3. Hydration
4. Ultrasound(physio & spots medicine- heating enhancing penetration
5. Iontophoresis (electrical driving of charged molecules into tissue)
6. Electroporation (creation of aqueous pores in the lipid by layers by the application of short electrical pulses) e-trans
7. Stratum corneum removal (laser ablation or adhesive tape)
8. Photomechanical wave (laser pulse that produces stress on horny layer enhancing drug delivery)
9. Needle array (injection of 400 micro needles that inserts drug just below the barrier)
10. Ion pairs (diffuse across horny layer to aqueous viable epidermis)
11. Complex coacervates (separation of oppositely charged ions to an oil phase)
12. Liposomes and transfersomes
-liposomes: form vesicles that can entrap and deliver drugs
through skin
-transfersomes: special type of liposome that incorporates edge
‘edge activators’ and can squeeze through pores
13. High-velocity particles (supersonic shock wave of helium gas)
14. Penetration enhancers (accelerants or sorption promotors that temporarily deminish the in permeability of the skin)

Question 3

List 10 examples of penetration enhancers or scorpion promoters (5)

Answer 3

Accelerants or sorption promotors that temporarily diminish the Impermeability of the skin.

1. Water
2. Sulphoxides
3. Pyrrolidones
4. Fatty acids and alcohols
5. Azone
6. Surfactants (anionic, cationic and non-ionic)
7. Urea
8. Alcohols and glycols
9. Essential oils, terpenes
10. Natural moisturising factor (NMF)

Question 4

Describe the manner in which accelerants or sorption promoters illicit their action (3)

Answer 4

Accelerants act in one or more ways:

1. Lipid action: disrupt the lipid structure of the stratum corneum making it more permeable to drugs
2. Protein modification: interact with keratin opening up its dense structure making it more permeable
3. Partitioning promotion: use of a co-enhancer or cosolvent

Question 5

Explain the concept of iontophoresis and how this process is utilised in transdermal drug delivery (4)

Answer 5

Is the electrical driving of charged molecules into tissue. Procedure involves passing a small direct current through a drug containing electrode that is in contact with the skin. A grounding electrode place on another part of the body completes the circuit.

Question 6

Discuss the applications and potential limitations to transdermal drug delivery (10)

Answer 6

Avoid GI difficulties 
Substitute for oral when oral is unadvisable
Avoid first pass metabolism 
Non invasive 
Extended therapy 
Short half life 
Terminates quickly 
Easily and rapidly indentified 

Limitations
Only potent drugs are suitable
Contact dermatitis

Question 7

Describe the technology and device design inherent to transdermal drug delivery systems. May refer to a specific commercial product to illustrate answer (7)

Answer 7

Device design:
-Monolith or matrix system:
An occlusive backing layer protects the drug matrix, which
comprises of a suspension of drug in equilibrium. An adhesive
layer contains dissolved drug and attaches the patch to the skin
-Rate-limiting membrane system:
A backing layer with drug reservoir containing drug in membrane
and a skin adhesive. On storage the drug equilibrates into the
membrane and adhesive allowing it to be more readily released.
This is called a burst effect which is quick acting and priming
dose of drug .