Skin

Question 1

Three layers of the skin and their thickness

Answer 1

Epidermis- 100 microns
Stratun Corneum- 10 microns
Dermis- 1000 microns

Question 2

What is the Stratum corneum (SC)?

Answer 2

The brick wall layer

Made up of corneocytes (brick) and corneodesmosomes (rivets) and mortar (complex lipid mixture)

Prevents water loss

Question 3

Pathways through SC

Answer 3

Transcellular- striaght through cells
Intercellular- around cells through ‘mortar’
Follicular- through hair follicles
Eccrine- through glands in the skin

Question 4

Jmax=(Ksc/v D/h) x Csatv

Explain this equation

Answer 4

Ficks law of maximum diffusion

Jmax=max diffusion
Ksc/v=SC/vehicle partition Coefficient of drug
D=diffusivity in membrane
h=diffusion path length
Csatv=saturation concentration of drug in vehicle

Question 5

Why is the previous equation shortened to Jmax=D/h x CsatSC?

Answer 5

Under ideal circumstances Jmax can be independant of vehicle so it is removed from equation

This however assumes vehicle does not alter SC properties or the drug conc in SC

Question 6

logKp= -2.7+(0.71x logP)-0.00061x MW)

What is this equation and why does Guy love it so much?

Answer 6

Him and his mate invented it

Its predictive of the permeability coefficient

Question 7

What does introducing a co solvent do?

Answer 7

Increases Csatv (solubility in vehicle) but decreases Ksc/v (the partition coefficient)

Therefore it is predicted that there will be a decrease in flux when % of cosolvent> the level required to just completely dissolve the drug

Question 8

Effects of physiochemical properties on bioavailability

Answer 8

Increasing lipophilicity gives greater flux (to an extent)

Jmax decreases with increasing MW

Question 9

Rtotal=Rsc +Red

Explain this equation

Answer 9

This calculates total resistance

Rsc= resistance of SC
Red= resistance of epidermis

Rsc»Red therefore Rsc is rate determining factor

Question 10

Effect of pH on percutaneous drug delivery

Answer 10

Skin is acidic so non ionised drugs most easily absorbed

Really high/low pH is pretty damaging to skin

Therefore pH is usually kept near neutral

Question 11

Formulation preferred for chronic skin conditions

Answer 11

Hydrocarbon based formulations preferred for occlusive properties

However not very good for topical drug delivery due to poor drug solubility

Solubility can be enhanced with solvents like isopropyl myristate or propylene glycol

Question 12

4 water free formulations

Answer 12

PEG gel- 1 phase, semi solid, polar

Lipogel- 1 phase, semi solid, polar, based on triglycerides

Oleogel- 1 phase, semi solid, polar, triglyceride+ hydrocarbon+ inorganic filler

Fatty ointment- 1 phase, semi solid, non polar, hydrocarbon based

Question 13

Polar gel formulations

Answer 13

Water/alcohol based can low lipid or lipid free

Can be made into emulsions (emulsion gel) and suspension gels

Not good for occlusive treatments (eczema/psoriasis)

Question 14

2 types of gel formulations

Answer 14

Hydrogel- semi solid, made of large organic mlecules interpenetrated by water

Emugel- 2 phase, semi solid similar to the above but with a small fraction of emulsified lipids

Question 15

Creams (emulsions)

Answer 15

Adjustable

Requires stabilisers

Dispersion is effected by emulsifier films at the oil/water interface

Question 16

Effect of w/o compared to o/w

Answer 16

w/o has higher F as it blends easier with SC lipids

but o/w is preferred by patients as it isn’t sticky/greasy

Also provides cooling effect as aqueous continuous phase evaporates but can withdraw moisture from skin due to surfactant like emulsifiers

Question 17

2 types of w/o creams

Answer 17

w/o lotion- hydrohobic, semi liquid, 2 phase

w/o cream- hydrophobic, semi solid, 2 phase

Question 18

Post administration formulation metamorphosis

Answer 18

Evaporation of solvent can change drug solubility in residual phase

This usually leads to an increase in thermodynamic activity until saturation is reached

At this point either supersaturation occurs or a reduction in permeability

Question 19

Drug delivery to targets below the skin

Answer 19

Eg NSAID’s

Has lower systemic circulation therefore less side effects