I have 10 questions but you can help answering it short but concise.

Question

1. If excipients do not have pharmacodynamic activity, how do excipients affect the performance of the drug product?

2. What is meant by the rate-limiting step in drug bioavailability from a solid oral drug product?

3. What is the usual rate-limiting step for a poorly soluble and highly permeable drug (BCS 2)?

4. How could the manufacturing process affect drug product performance?

5. Drug absorption involves at least three distinct steps: dissolution, permeation, and disposition during transit in GI (an additional step of drug disposition in the body is involved as well for bioavailability). How are these processes validated in vitro when the in vivo requirement for drug bioavailability is waived?

6. What is meant by “sink” conditions?

7. What physical or chemical properties of a drug substance are important in designing a drug for (a) oral administration or (b) parenteral administration?

8. For a lipid-soluble drug that has very poor aqueous solubility, what strategies could be used to make this drug more bioavailable after oral administration?

9. For a weak ester drug that is unstable in highly acidic or alkaline solutions, what strategies could be used to make this drug more bioavailable after oral administration?

10. Why can two generic drug products have different dissolution profiles in vitro and still be bioequivalent in vivo?

Note: These are under Biopharmaceutics but there's no option of the subject here, sorry. Hope you can help me,

Answer 1

1- It affects ionization of drug and eventually ABSORPTION

2- Drug to be absorbed it must be 90% non ionized. A rate limiting step it the reaction which changes pH of stomach to affect ionization of drug to 10% or so.

3- According to the structure of of cell membrane; electrophilic from outside and inside and lipophilic from inside, poorly soluble drug will not be absorbed.

4- changing the physiochemical character... size by nano, liposomal carrier, ionization ..... etc

5- dissolution is by solubility in liquids with different pH and analytical measured by HPLC

Permeation on dialysis bag or Permeation Analyzers

Disposition by flow of solution (biological) to have an even distribution of equal concentration

6- Sink is a term to It means using a sheer volume of solvent, usually about 5 to 10 times greater than the volume present in the saturated solution of the targeted chemical i.e. describe unvoluntary control to move ions from one side to another e.g. electron sink

7- Molecular weight of drug. Drug Formulation (ease of dissolution), (solution > suspension > capsule > tablet). Drug solubility , Chemical stability in gastric pH (Penicillin & insulin ) and  First pass metabolism reduces bioavailability

8- Either using nano technology to affect the size, liposomal formula or chemically adding an ionizable group to the molecule

9- Coating

10- Excipient effect