Delivery to Skin

Question 1

Skin innervation - 6

Answer 1

1. Meissner receptors detect light touch.
2. Pacinian corpuscles perceive deep pressure & vibrations.
3. Ruffini endings detect deep pressure & stretching of the skin’s collagen fibres.
4. Merkel’s discs used to reconstruct acute spatial images of tactile stimuli.
5. Krause bulbs detect cold temperatures.
6. Free nerve endings respond to pain, light touch, & temperature variations

Question 2

Stratum Corneum - 4

Answer 2

1. Major water barrier of the skin - prevents trans epidermal water loss(TEWL)
2. Brick & mortar type structure
3. Brick - Dead keratin-filled cells
4. Mortar - Complex lipid mixture

Question 3

corneodesmosomes - 3

Answer 3

1. modified desmosomes holds together corneocytes (dead skin cells) in the stratum corneum. Essential for: barrier integrity
2. Degraded for desquamation of skin - proteolytic enzymes in epidermis controls rate & extent of corneocyte exfoliation.
3. If impaired can cause inflammatory skin disease

Question 4

What objectives are there for topical drug therapy - 4

Answer 4

1. Modulate barrier function
2. Treat disease states in the epidermis and dermis
3. Alleviate local pain/inflammation in the SC tissues
4. Elicit systemic pharmacological effect

Question 5

What is percutaneous absorption and what is it dependant on - 5

Answer 5

1. Drug penetrates skin, cannot be removed by washing,
2. Drug taken up by microcirculation, so drug either enters systemic circulation or carried to deeper tissues beneath the skin.
   Dependant on:
3. Physiochemical properties
4. Drug-vehicle-skin interactions
5. Condition of the skin

Question 6

Fick’s law

Answer 6

C to power sat multiplied by v
e.g.
C power sat SC = [Saturation of drug in stratum corneum]
C power sat w = [Saturation of drug in water]

D = diffusivity of drug in membrane
Ksc/v = SC/vehicle partition coefficient of drug
h = diffusion path length across SC

Fick’s law used to predict max flux across skin

Question 7

Co-solvent - 2

Answer 7

1. Many topical drugs are lipophilic with very low aqueous solubility.
2. Introduction of co-solvent into a formulation can significantly increase the Csatv but will have the opposite impact on Ksc/v

Question 8

How can topical BA be measured In vitro, silico & vivo - 7

Answer 8

In vitro
1. Methodology and data analysis
2. Permeability coefficient, % dose absorbed

In silico
3. Permeability coefficient
4. Maximum flux calculation

In vivo
5. Pharmacodynamic measurement {vasoconstriction assay}
6. Stratum corneum tape-stripping {dermatopharmacokinetics}
7. Micro dialysis

Question 9

How does pH of vehicle play a role in skin delivery - 2

Answer 9

1. Skin surface pH is acidic, 4 - 5.5, so unionized drugs best absorbed
2. Extreme pH values can damage skin; so formulations mostly neutral

Question 10

What resistances are there to percutaneous transport - 2

Answer 10

1. After SC, drug must still cross viable epidermis & upper dermis to reach microcirculation
2. e.g. Stratum corneum is rate-determining barrier
   Except for very lipophilic drugs which partition out of the SC very slowly

Question 11

Skin permeation enhancers

Answer 11

Some excipients can improve drug flux, but skin irritation can be an issue