Biopharmaceutics

Question 1

What is biopharmaceutics?

Answer 1

Study of factors affecting the rate and extent of drug absorption – PROBLEMS WHICH FORMULATION MUST OVERCOME TO MAXIMISE EFFICACY OF DRUG.
These factors ultimately will determine how fast and how much of the drug is available in the blood.
Bioavailability ‘F’
Clinical effect is proportional to the plasma drug concentration.

Question 2

What are the physiological factors influencing drug absorption in the GI tract?

Answer 2

Surface area of absorption sites
pH of GI fluids
Gastric emptying rate
Intestinal motility
Chemical degradation in GI tract
Liver metabolism
Diet

Question 3

What are the physicochemical factors of the drug?

Answer 3

Solubility and dissolution
Lipid solubility and log P
Molecular weight

Question 4

What types of dosage forms influence drug absorption?

Answer 4

Aqueous solution
Aqueous suspension
Soft gelatin capsule
Hard gelatin capsule
Uncoated tablet
Coated tablet
Enteric coated/gastro- resistant tablet

Question 5

What are the two absorption processes?

Answer 5

Passive diffusion
carrier mediated transport

Question 6

What are the two absorption processes?

Answer 6

Passive diffusion
carrier mediated transport

Question 7

What are the 5 different absorption pathways?

Answer 7

Passive diffusion
Carrier mediated
Transcytosis/ Pinocytosis
Ion pairing
Pore transport

Question 8

What is passive diffusion?

Answer 8

Lipid soluble drugs are more easily absorbed through the membranes than water soluble drugs
Determined by physicochemical properties of drug, i.e. log P, nature of the membrane and concentration gradient

Question 9

The drugs permeability across the GI for passive diffusion is determined by what?

Answer 9

Fick’s first law dm/dt=PCg

dm/dt is the rate of appearance of drug in blood (absorption)
cg is the drug conc in GI fluid
P is permeability constant

Question 10

What is different about carrier-mediated transport?

Answer 10

Carrier-mediated transport is different in that it is specific (only drugs with specific structures which resemble structures of endogenous substances can be taken up) and energy dependent (uses up energy to take place) and against concentration gradient (passive diffusion occurs along concentration gradient).

Question 11

When the absorption rate decreases what happens to the amount of drug in the GI fluid? What order of kinetics does it follow?

Answer 11

Absorption rate tends to decrease as the concentration of drug in GI fluid decreases, i.e. follows first order kinetics.

Question 12

Why do we formulate? and what is considered?

Answer 12

Formulation is a means to maximise the ‘F’ of drugs in order to provide maximum benefit to patients.
To do this we have to consider:
Patient, i.e. provide dosage form for patients to maximise compliance.
Drug properties and physiology, i.e. maximise stability, solubility and permeability.
Disease, i.e. maximise efficacy of drug by ensuring drug reaches site of action.

Question 13

What is the order of decreasing bioavailability of each dosage form, ( uncoated tablets, coated tablets, aqueous suspensions, aqueous solutions and capsules)

Answer 13

Aqueous solutions > aqueous suspensions > capsules > uncoated tablets > coated tablets

Question 14

1. Explain what is meant by the terms biopharmaceutics and bioavailability.

Question 15

2. Discuss the various physiological factors influencing drug absorption from the GI tract, such as:
   a. surface area of absorption sites
   b. pH of GI fluids
   c. gastric emptying rate
   d. intestinal motility
   e. chemical degradation in GI tract
   f. liver metabolism
   g. diet

Question 16

3. Discuss the physicochemical factors involved in drug absorption, such as:
   a. Drug solubility and dissolution rate – including effect on this of particle surface area and whether the drug is a weak electrolyte
   b. Forms of the drug – salt forms, polymorphs, amorphous, crystalline, solvates and hydrates.
   c. Lipid solubility and Log P.

Question 17

4. Discuss the use of the Biopharmaceutics Classification System (BCS) to predict oral drug bioavailability.

Question 18

5. Describe the pH-partition hypothesis including its limitations.

Question 19

6. Discuss the two most common mechanisms of drug absorption: passive diffusion and carrier-mediated transport.

Question 20

7. Describe how the use of different excipients, such as diluents, surfactants and viscosity enhancing agents in dosage forms, can influence drug dissolution and absorption.

Question 21

8. Describe how the choice of the type of dosage form, such as aqueous solutions, suspensions, gelatin capsules, coated and uncoated tablets, can influence drug dissolution and absorption.