Sustained release etc.

Question 1

What are three reasons which could lead to their being a lower value of F or a SR formulation versus the immediate release version?

Answer 1

1. Too slow release of the drug. Drug is released beyond the absorption window.
2. The permeability of the drug becomes too low when it is released, or the dosage form is voided before complete release takes place.
3. Solubility problems etc.
4. The drug is a substrate for p-GP etc and released too late.
5. The drug suffers saturable (non-linear) first pass effect.

Question 2

How will the AUC differ for a SR and IR formulation of a drug?

Answer 2

The AUC should remain similar as even though the max C is lower, they are present for longer and hence the added area/time compensates for lower C.

If the AUC is lower this could indicate that F is lower for the sustained release formulation due to:

1. Too slow release of the drug. Drug is released beyond the absorption window.
2. The permeability of the drug becomes too low when it is released, or the dosage form is voided before complete release takes place.
3. Solubility problems etc.
4. The drug is a substrate for p-GP etc and released too late.
5. The drug suffers saturable (non-linear) first pass effect.

Question 3

How will B (the rate constant of the terminal phase) differ between IR and SR formulations?

Answer 3

SR:
Typical of SR to observe flip-flop kinetics. Release and absorption are so slow that they become rate-limiting, so the constant controlling the decline of the plasma concentration is not the elimination rate but the absorption rate constant.

Question 4

How will the Tmax and Cmax differ between IR and SR formulations?

Answer 4

For SR:

Tmax will be higher, Cmax lower.

Question 5

What are the key advantages of oral sustained release formulations?

Answer 5

1. Extend time during which C is in the therapeutic range.
2. Avoid high peaks, avoiding toxicity.
3. Avoid C below C min.
4. Extend interval of administration, decreasing dosing frequency facilitating compliance.
5. Can be used for drugs with short half-life.

Question 6

How does the pH change as you progress along the GI tract?

Answer 6

Stomach: 1-2
Duodenum: 5-6
Ileum = 7-8
colon = 5.5 - 7