6. Skin Penetration & Drug Delivery (Topical Absorption)

Question 1

Main barrier in absorption

Answer 1

• Stratum Corneum (SC)

- SC densely packed with keratinised skin cells (brick & mortar structure)

Question 2

Permeation pathways (3)

Answer 2

1. Transcellular (across cells)
2. Intercellular route (between cells)
3. Transappendageal route - through hair follicles, sweat glands & sebum glands

Question 3

Passive diffusion

Answer 3

• Movement of the drug into the deeper layers of the skin following random molecular motion
• The transfer rate of diffusing drug is proportional to the concentration gradient

Question 4

Fick’s 1st Law of Diffusion

Answer 4

J = DCoK/h

J (dm/dt): Mass transferred per unit area per second (mg cm-2 h-1)

Question 5

Ideal drug properties for topical drug delivery

Answer 5

• Low molecular weight
• Balanced partition coefficient (log P of 1-3)
• Adequate solubility in oil & water
• Low melting point (<200 degrees)
• Must be highly potent
• Must not irritate the skin

Question 6

Physicochemical factors affecting drug permeation

Answer 6

• Molecule size & structure
• Partition coefficient (1-3)
• Permeability coefficient
• Diffusion coefficient
• Solubility
• Particle size
• pH & pKa

Question 7

Biological factors affecting drug permeation

Answer 7

• Anatomical site (area)
• Age
• Skin hydration
• Skin temperature
• Skin pathological condition

Question 8

Formulation factors affecting drug permeation

Answer 8

• Drug properties
• Drug concentration
• Drug release formulation
• Delivery system
• Penetration enhancers

Question 9

Transdermal delivery

Answer 9

• Delivers the drug past skin to reach the circulation & exert a systemic effect

Question 10

Topical delivery

Answer 10

• Delivers the drug into the skin to treat skin disorders (epidermal or dermal) - target organ is the skin

Question 11

Enhancement of topical delivery

Answer 11

• Remove stratum corner using chemical or inhibition of proteolytic activity to increase delivery of charged hydrophilic molecules
• Use penetration enhancers
• Use advanced dosage forms e.g. micro emulsion to enhance delivery of hydrophilic compounds across skin

Question 12

Advantages of Topical Drug Delivery

Answer 12

• Avoids 1st pass metabolism
• Easy application
• Reduced side affects
• Reduced drug dosing (controlled release)

Question 13

Disadvantages of Topical Drug Delivery

Answer 13

• Only suitable for drug molecules with specific physicochemical properties that does not irritate skin
• Variability
• Permeability of intact & broken skin
• Skin irritation & sensitisation
• Skin is a barrier for drug absorption

Question 14

Penetration enhancers

Answer 14

Chemical enhancers e.g. surfactants modify the barrier properties of the SC to enhance drug permeation & absorption

Physical enhancers:

• Ultrasound
• Iontophoresis
• Electroporation
• Sonophoresis
• Microneedles

Question 15

Chemical penetration enhancers - ideal characteristics

Answer 15

• Reversibly reduce barrier resistance of SC without damaging cells
• Non-toxic, non-irritating & non-allergenic
• Work rapidly
• Have no pharmacological activity in the body
• Cosmetically acceptable with appropriate skin feel

Question 16

Commonly used chemical penetration enhancers

Answer 16

• Water
• Alcohol
• Fatty acids
• Surfactants
• Urea

Question 17

Mechanism of chemical penetration enhancers

Answer 17

• Polarity alteration
• Lipid extraction
• Phase separation
• Fluidisation
  (all affect the phospholipids in the bilayer)