General skin

Question 1

What is the role of the stratum corneum?

Answer 1

Mechanical cushioning to make skin robust - barrier

Regulation of water loss

Question 2

What part of the epidermis goes wrong when you get:

• eczema
• psoriasis

Answer 2

Eczema - stratum corneum

Psoriasis = stratum basale due to hyperproliferation

Question 3

What forms the stratum corneum?

Answer 3

Basal cells divide, migrate outwards and differentiate, then flatten to form the stratum corneum. (when basal cells divide they lose their nucleus and then they become filled with keratin)

Question 4

What cells are the immune cells in the epidermis?

Answer 4

Langerhans cells which are dendritic cells - process microbial antigens.

Question 5

What is the UV shield in the epidermis?

Answer 5

The malanocyte cells containing melanin pigment which is taken up by keratinocytes to protect from UV radiation

Question 6

What is the role of keratinocytes?

Answer 6

Protection - produce keratin which is a fibrous protein helps give epidermis protective properties

Question 7

What happens when there is a filaggrin mutation?

Answer 7

Reduced Natural moisturising factor and thus the skin is drier, loss of integrity and is a risk factor for hypersensitivity/allergy (IgE)

Question 8

Where are the. sweat ducts, sebaceous glands, sweat glands, hair follicles contained in the skin?

Answer 8

Dermis

Question 9

What cells are. the sensory receptors?

Answer 9

Merkel cells - they have. sensory nerve endings. for touch

Question 10

What are the 2 types of sweat gland?

Answer 10

Eccrine (e.g. prevent body overheating, gland ducts empty. into pores which lead to the skin surface)
Apocrine (e.g. nipples, armpits, eyelids) - secrete fatty exudate, empty in hair follicles. Blocked in acne.

Question 11

What part of the. skin is implicated in acne?

Answer 11

Sebaceous oil glands- sebum secretion is under. hormonal control

Question 12

What is transdermal drug delivery?

Answer 12

Delivery across the skin for SYSTEMIC action

Question 13

What is local drug delivery?

Answer 13

Delivery of drug at the site of action - so it acts at the site at which it is applied

Question 14

What is topical drug delivery?

Answer 14

Acts at a site in the skin e.g. epidermis/dermis

Question 15

What is the biggest barrier to drug delivery?

Answer 15

Outer stratum corneum - rate limiting structure for most drugs is multiple. lipid bilayers. Hence need the drug to be lipophilic

Question 16

What are the 2 key aspects of drug formulation that drugs should have?

Answer 16

Lipophilic - better delivered

Lower MP - better absorbed

Question 17

Some advantages of transdermal delivery

Answer 17

Easy cessation if need, large surface area, avoids 1st pass metabolism

Question 18

What is the main route of drug delivery to skin?

Answer 18

Intercellular predominates at steady state

Question 19

What type of formulation would you use if you had:

• oily
• normal-dry
• dry

Answer 19

oily - gel - water base
Lotions for normal/dry

Dry - creams

Question 20

What type of. formulation would you use if you had:

Hairy site

Answer 20

Lotions, gel, spray

Question 21

What type of. formulation would you use if you had:

a wet, vesicular, weeping lesion

Answer 21

Wet aqueous based - cream, lotion, gel

No alcohol

Question 22

What type of. formulation would you use if you had:

Dry, thickened, scaly lesion

Answer 22

Dry fatty e.g. ointment / paste

Question 23

What are the ideal drug candidate properties for delivery and what does it not account for?

Answer 23

Mwt 300-500
LogP 1-3.5 lipophilic
Aq solubility >100mg/mL. some

Does not account for potency

Question 24

If you wanted to deliver a drug:

for extended delivery through the skin - what would you. use?

Answer 24

Transdermal patch

Question 25

If you wanted to deliver a drug: for increased residence on the skin - what would you use

Answer 25

Semi solid

Question 26

If you wanted to deliver a drug: for rapid short term input of drug into skin - what would you use

Answer 26

Liquid

Question 27

what do we assume drives diffusion of drugs across the membrane? how do we show this?

Answer 27

Thermodynamic activity - shown as Flux equation, use of franz cells So concentration is not relevant, it is more important to focus on thermodynamic activity

Question 28

What is the role of emollients?

Answer 28

Moisture, trap in moisture by forming a protective film | e.g. diprobase, E45

Question 29

Why is alcohol useful excipient (provided the SC is in tact)?

Answer 29

It can enhance delivery via volatilisation and supersaturation - good solvent for. lipids and drugs must e lipophilic to get through SC

Question 30

What is the bioavailability of: - topical products - patches

Answer 30

Topical 1-3 % F | Patches 30-70% F

Question 31

What do saturated solutions do?

Answer 31

Have maximum thermodynamic activity to maximum diffusion and thus can even use low concentrations of saturated solutions to deliver drug

Question 32

What is occlusion?

Answer 32

The Stratum corneum equilibrates with the underlying wet dermis to stop trans-epidermal water loss but can cause irritation

Question 33

What do enhancers do? | Give examples

Answer 33

They interact reversibly with the skin to promote drug flux - they disrupt the SC lipid structure which is crystalline to get hydrophilic drugs through examples are solvents e.g. ethanol, PPG, surfactants SLS, fatty acids e.g. oleic acid, hydrotropes e.g. urea.

Question 34

In a drug in adhesive patch - does the size relate to the dose delivered?

Answer 34

Yes - Surface area M^2. Drug is in a rate limiting membrane. If the patch is bigger it has a larger surface area and more delivered

Question 35

What other ways can you deliver drugs via skin and improve delivery?

Answer 35

Micelles nanoparticles, ethasomes liposomes - they enhance the permaation of lipophilic drugs, fuse with surface and increase thermodynamic activity to increase drug content to tissue and have a reservoir effect

Question 36

What is a drug that causes occlusion that is bad?

Answer 36

Steroids - because they can have a rebound effect, get blanching. Steroids cause vasoconstriction so skin will go white (blanch) then if you cover the site a day later with something occlusive - rebound blanching. Water increases in SC and kicks steroids off the capillaries and they drug stay in the SC

Question 37

when someone puts a cream on - where is the drug really being delivered from?

Answer 37

when you rub a cream in it undergoes metamorphosis, so drug comes. from residue of the formulation rather than the actual cream as you are rubbing the cream in

Question 38

What type of patch can you cut? | what can. you cut?

Answer 38

if it is in a liquid reservoir you cannot cut it Drug in adhesive you can cut

Question 39

What is a liposome?

Answer 39

Hydrophilic heads and lipophilic tails - contain hydrophilic drug and get through lipophilic membrane, enhancing diffusion and absorpion