Week 9 - Transplants (transdermal delivery)

Question 1

Transdermal Delivery BASICS

Answer 1

• Transdermal delivery penetrates further into skin (into blood circulation)
  
  • in comparison to creams + ointments that deliver to surface layer of skin
• Non-invasive used to treat many conditions e.g. migraines, diabtes, contarception / hormonal imbalance, motion sickness, smoking cessation

Question 2

Why is the skin a barrier to the passage of molecules across the skin

Answer 2

Skin is designed to keep micro-organsims, chemicals etc. out of the body

MAIN BARRIER = Stratum corneum
- consists of dead keratin cells held by lipid bilayer

Question 3

Whats the difference betweeen drugs stored in: adhesive system, a matrix and a reservoir

Passive Transplants

Answer 3

1. Reservoirs:
   
   • have rate controlling membrane that seperates drug layer from adhesive layer
   • membrane controls release of drug
   • drug - membrane - adhesive layer
   • NOTE: NEVER CUT them
2. Matrix:
   
   • dont have membrane (just drug layer then adhiesive layer
   • adhesive layer surrounds drug layer
   • drug release is controlled by matrix physical properties
   • NOTE: can be cut
3. Adhesive System:
   
   • drug is stored in the adhesive layer
   • can have sinlge layer (liner + backing)
   • OR multi-layer (2nd layer sepearted by membrane) ~ 1st layer = immediate release of drug, 2nd layer = controlled release of drug

Question 4

List the 2 types of transdermal drug delivery systems

Answer 4

1. Passive patches
   
   • diffusion (of drug) from patch to skin + into body
2. Active patches
   
   • Use active method to transfer drug from patch + into skin / body
   • less commonly used
   • Breach skin barrier (permeability of stratum corneum) in 2 ways:
     1. Physical methods
     2. Electrically assisted methods

Question 5

How do Passive patches exert their therapeutic effect

Answer 5

Deliver drug via diffusion

• Remove liner / backing from adhesive layer
  
  • liner is in contact with environment
  • protects patch during storage + from environment
• Place patch adhesive layer onto skin
  - adhesive layer allows patch to stick to skin
• Rate controlling membrane
  - controls rate drug is released from reservoir
  - controlled constant rate of drug delivery

Question 6

What are the proeprties of passive patches

Answer 6

• Low MW (< 1000 Da)
• Low melting point
• Few OH groups
• Few polar centres
• Low partition coefficient (1-3)
• Short half life (< 6 to 8hrs)
• Low dose drug (5-20mg)

Question 7

What are the advantages of passive patches

Answer 7

• Painless
• Improved pt compliance (its discreet)
• No fluctuations in drug conc.
  - no peaks and torughs
  - have steady state conc. of drug
  - gradual increase then steady state
• Non-invasive
• Less risk of infection
• Can terminate therapy by removing patch
  - gradual or rapid decline in conc. depending on drug
• Suitable for pts vomiting, diarrhoea
• Bypasses 1st pass metabolism

Question 8

What are the disadvantages of passive patches

Answer 8

• Limited no. of drugs can be incorporated into patches
• Skin irritation / allergy reactions
• Lag time before therapuetic effects are reached
  = may need to start oral dose first or at same time to get to blood conc. up quick
• Poor peripheral circulation = slow drug absorption
• Not suitable for tolerance inducing drugs
• Drug needs to be soluble in both lipophilic and aqueous (hydrophillic) environments)

Question 9

What are the 4 “electrically assisted methods” active patches exert their therapeutic effect

Answer 9

1. Ultrasound (US)
   
   • US waves fluidises the lipid bilayer in skin = move around more + bubbles form which implode = gaps
   • gaps allow drug to pass
2. Iontophoresis
   
   • Have 2 electrodes
   • Apply small electric current to drug (with one electrode ~ has same charge as drug)
   • Counter electrode goes on skin
   • Drug is driven away from cathode into skin when current is turned on (repulsion drives drug into skin)
   • temporarily disrupts skin permeability
3. Reverse Iontophoresis
   
   • Doesnt drive anything into skin, instead TAKES glucose OUT of body
   • Used for blood glucose monitoring
4. Electroporation
   
   • Creates aqueous pores in lipid bilayer of skin (stratum corneum)
   • Use high voltage in short pulses = rearranges lipid formation = pores form
   • Pores allow large molecules into body e.g. proteins

Question 10

What is the “physical method” active patches exert their therapeutic effect

Answer 10

Microneedles

• Micron sized needles which pierce the stratum corneum creating many small holes
• Drug can pass thrugh these holes

NOTE:
- Pt needs to apply presure when sticking patch = hard to get correct force to get needles to go deep enough

Question 11

What are the advantages of active patches

Answer 11

• Painless (physical method)
  
  • needles dont go far into skin to interact with pain receptors

Question 12

What are the disadvantages of active patches

Answer 12

• Breachind skin barrier can allow other things (that are not meant to be in the skin) enter into the skin