Influence of biopharmaceutical factors on dosage form design (07/02/19)

Question 1

What are the key steps in absorption?

Answer 1

1. Dissolution

2. Permeation =cross epithelial wall into blood or lymphocytes

Question 2

What are the key competing processes?

Answer 2

1. Transit = removal of dosage form before absorption

2. Stability = break down of drug in gut lumen, gut wall or by liver before reaching blood

Question 3

What is the Biopharmaceutics Classifiaction System (BCS) criteria and limitations?

Answer 3

1. Solubility = max dose strength in 250ml or less over pH1-8
2. Permeability = over 90% absorption

Limitations: stability at diff. pH, and binding interaction with gut or contents

Question 4

What are the different Classes in Biopharmaceutics Classification System?

Answer 4

1. Class 1 = high solubility, high permeability
2. Class 2 = low solubility, high permeability
3. Class 3 = high solubility, low permeability
4. Class 4 = low solubility, low permeability

Question 5

Example of Class 1 drug?

Answer 5

Propanol

Question 6

Example of Class 2 drug?

Answer 6

Ketoprofen

Question 7

Example of class 3 drug?

Answer 7

Atenolol, gabapentin

Question 8

Example of class 4 drug?

Answer 8

furosemide

Question 9

What is the pH of gastric fluid (both fasted and fed)?

Answer 9

Fasted = 1-3.5

Fed = 3-7 (residence time longer)

Question 10

When should you take a drug with/after meals?

Answer 10

If the drug is unstable in gastric fluid. (example = penicillin, omeprazole, erythromycin

Question 11

What is required to measure absolute bioavailability?

Answer 11

Requires measurements of blood plasma drug conc vs time (AUC) after extravascular dosing and after IV administration of drug.

Question 12

What is required to measure relative bioavailability?

Answer 12

Plasma AUC of a test dosage is compared to a standard dosage form. Both administered by same extravascular route (e.g., oral)

Question 13

A drug is considered bioequivalant if what factors are met?

Answer 13

‘Bioequivalent’ suggests that the test dosage form will have the same therapeutic effectiveness as the standard form.

Bioequivalent if NO significance difference in: AUC, Tmax, and Cmax

(Tmax and Cmax time at peak and drug concentration at the peak of the [Drug] vs time graph)