TD: Transdermal delivery

Question 1

Describe the layers of the skin

Answer 1

Stratus corneum is rate limiting step to transdermal drug delivery!!

Question 2

Describe approaches to drug delivery

Answer 2

1. Manipulate the barrier function of the stratum corneum. Emollients used - these form an occlusive layer over the stratum corneum preventing water loss. This causes swelling of the skin and allows greater permeability to drugs
   
   • antibacterials and antibiotics help a damaged barrier to ward off infection,
   • sunscreens and the ‘horny layer’ protect the viable tissues from UV radiation,
   • emollients restore pliability to a desiccated horny layer.
2. Direct drugs to the viable skin tissues without using oral, systemic or other routes of application
   • By pass first-pass metabolism
3. Skin delivery for systemic treatment
   
   • transdermal therapeutic systems provide systemic therapy for a variety of conditions
   • eg motion sickness, angina, smoking cessation, hormonal therapy etc.

Question 3

Give examples of some treatment options for:

1. Surface of the skin
2. Stratum corneum
3. Appendages
4. Viable epidermus and dermis
5. Circulation

Answer 3

Question 4

Advantages of transdermal delivery

Answer 4

• Primary objective is to deliver drugs systemically
  
  • ie direct to blood stream avoiding GI tract.
• GI delivery is hindered by digestive enzymes which can degrade drug before effective absorption
• GI delivery involves the ‘first-pass metabolism’
  
  • ie drugs metabolised by liver (potential damage).
• Continuous (steady-state) drug delivery is possible and desirable

Question 5

Disadvanatages of transdermal delivery

Answer 5

• Drugs must have some lipophillic character and low mwt
• Drugs must be extremely potent
• Skin irritation
• Stratum corneum provides rate-limiting step due to relatively imperveous properties.
• Delivery through skin is variable

Question 6

What apparatus can be used to test drug permeability?

Answer 6

Diffusion cell - tests drug permeability across a rate-controlling membrane

membrane can be real or synthetic

Question 7

What is Fick’s law of diffusion

Also read next slide

Answer 7

Fick’s Law describes the relationship between the rate of diffusion and the three factors that affect diffusion. It states that ‘the rate of diffusion is proportional to both the surface area and concentration difference between delivery system and membrane and is inversely proportional to the thickness of the membrane’.

Question 8

What factors affect skin permeabillity?

Answer 8

• Body site:
  
  • varying permeability
• Age of skin:
  
  • foetus, young & elderly have more permeable skin.
• Skin condition:
  
  • ​ damaged skin is more permeable e.g. acids, alkalis and solvents all damage skin and promote penetration whereas corns and calluses decrease penetration.
  • inflamed (loss of stratum corneum) abraded, cut burned or open skin leads to increased permeability.
• Metabolism:
  • skin is an active metabolic site and can oxidise, reduce, hydrolyse or conjugate drugs.
• Hydration :
  
  • the higher the hydration of the stratum corneum, the greater the permeability.
• Reservoir:
  
  • Drugs can accumulate in pockets effect (reservoirs) in the skin.

Question 9

What are formulation factors to consider?

Answer 9

• Drug solubility:
  
  • partitioning in favour of the over the vehicle is desirable.
• Influence of pH:
  
  • ionised and non-ionised forms of drug can permeate skin.
• Hydration :
  
  • lipophilic vehicles form occlusive layers on stratum corneum and prevent water escaping from sweat pores, emolliating skin.
• Drug Concentration :
  
  • higher drug concentration in concentration vehicle can result in increased drug absorption.
• Contact time:
  
  • the longer the product is in contact with the skin, the greater the absorption.
• Surface area
  
  • greater the area of application,the greater the absorption.
• Availability:
  
  • release of drug depends on from vehicle whether the drug is in solution, suspension or emulsion forms
• Penetration:
  
  • chemicals that reversibly enhancers compromise the skin’s barrier function and promote delivery.

Question 10

Method to enhance drug penetration

Answer 10

• Hydration:
  
  • water opens up the stratum corneum
• Ultrasound
  
  • ultrasonic energy disturbs the lipid packing in the intercellular spaces of the stratum corneum
• Microneedle
  
  • Stratum corneum by-passed by device consisting of 400 microneedles that insert drug just below stratum corneum.
  • Needles can be solid silicon and drug-coated or hollow metal with drug fill
  • Not painful.
• Electroporation
  • creation of pores in the lipid layers by the application of short microsecond electrical pulses.
• Penetration - very commonly used method of promoting skin enhancers permeability.
  
  • (DMSO), (DMF), DMA, ethanol,propylene glycol, surfactants, terpenes etc etc
• High velocity - PowderJectä system
  
  • pain free.
  • particles fire solid particle through the SC using supersonic shockwave of helium gas.

Question 11

Describe the difference between membrane and gradient reservoir systems for transdermal patches

Answer 11

Membrane - drug is uniformly contained within a matrix (hydrogel). As contact time increases drug depletion rate decreases in a non-linear fashion

Gradient - drug in matrix is varied with a graidnet - drug lowest conc at surface and highest at back= more constant delivery

Question 12

What are examples of transdermal patches and theri uses?

Answer 12

Question 13

Iontophoresis

Answer 13

Question 14

Iontophoresis

Answer 14

Question 15

Iontophoresis equation

Answer 15