P12

Explain why you want to start with max flux?

Can back off and if you have achieved max flux and still have no therapeutic effect then you need to change formulation

What follows ficks law?

Passive transport across the skin

What does the saturation of the drug do to flux?

If you saturate the drug in formulation, then you can’t get a flux higher than that

How can you define the SC/vehicle partition coefficient?

the most drug that can dissolve in the SC/ the most drug that can be dissolved in the Vehicle

How can Jmax be independent of the vehicle?

As long as the the drug is saturated in the vehicle the concentration in the SC will always be SC saturation, if the vechile does not change drug solubility in the SC

Define the vehicle type of a simple hydrogel?

Water, so the saturation of the vehicle = saturation concentration of the drug in water

What does kp stand for?

Permeability coefficient, units are those of speed

How does kp simplify jmax calculations?

Can use a predictive algorithm using the log P and MW, look up saturation concentration of the drug and can multiply those value together

What happens to jmax with increasing MW?

Decreases

Why can we think of D/h as a constant?

The vehicle is unlikely to change the diffusivity of the drug across the SC unless something has been added to disrupt lipids

What is the saturation concentration of the vehicle based on?

How much the drug likes the formulation, by changing this we can change the partition coefficient

How can we increase saturation concentration in vehicle of lipophilic drugs?

Adding a cosolvent such as PEG

What is the disadvantage of adding PEG to a formulation?

It may increase Cin vehicle it has the opposite effect on partition coefficient

Why doe the addition of PEG have no influence on saturation concentration in SC?

As it stays the same no matter what vehicle

What 3 ways can you try and improve topical bioavailability?

in vitro, in silico, in vivo

Describe the In vitro method?

Skin from plastic surgery or pigs, can do methodology and data analysis

Describe the In silico method?

Using permeability coefficient and max flux calculation to make predictions

Describe the In vivo method?

Via vasoconstriction assay, SC sampling, microdialysis

Define total resistance in percutaneous transport?

Drug has other skin layers to cross after SC to reach micro circulation, this all of them added up SC usually rate limiting

How does pH affect absorption?

Skin surface acidic so unionised drugs best absorbed

What is lag time?

The time take to reach linear concentration gradient never from time 0