Disintegration/Dissolution

Question 1

How is diffusion pharmaceutically relevant? How is free diffusion involved in pharmaceutically related processes?
(3)

Answer 1

1. dissolution of drugs from tablets/capsules/powders/granules
2. drug release from ointments/suppositories
3. permeation and distribution of drug in living tissue

Question 2

What 3 processes are necessary for the drug in a solid oral dosage form to become bioavailable?

Answer 2

1. disintegration
2. dissolution
3. absorption

Question 3

flux (J)

Answer 3

mass of material flowing through a unit cross-section per unit time

proportional to concentration gradient

Question 4

diffusivity (D) is affected by changes in:

Answer 4

concentration, temperature, pressure, solvent

Question 5

Fick’s First Law

steady state diffusion

Answer 5

describes mass of material flowing through a unit cross-section per unit time

concentration gradient does not change (steady state)

Question 6

Fick’s Second Law

non-steady state diffusion

Answer 6

describes change in concentration through a unit cross-section per unit time

concentration gradient does change (non-steady state)

Question 7

How is dissolution pharmaceutically relevant? What does dissolution rate affect?
(4)

Answer 7

1. onset of action
2. duration of action
3. extent of action
4. overall bioavailability, sometimes

Question 8

Factors that influence dissolution rate:

Answer 8

• physical/chemical properties
• particle size
• pKa/pH/ionization
• crystalline structure
• excipients
• dosage form

Question 9

Noyes-Whitney equation

Answer 9

measure of dissolution rate in terms of surface area

Question 10

Hixson-Crowell Cube Root Law

Answer 10

measure of dissolution for uniform powders in terms of particle mass

Question 11

pH-partition coefficient hypothesis

Answer 11

For drugs that are absorbed from the GI tract via passive diffusion, absorption depends on the proportion of unionized drug at the pH of the site of absorption (intestines)

Question 12

modified Noyes-Whitney equation

Answer 12

demonstrates how many variables can affect drug dissolution

Question 13

How can we maximize drug dissolution?

Answer 13

By minimizing dissolved drug concentration in the intestines (high drug concentrations increase absorption)

Question 14

simulated gastric fluid

Answer 14

pH 1.2

NaCl, HCl, DI water

Question 15

simulated intestinal fluid

Answer 15

pH 6.8

KH2PO4, NaOH, DI water

Question 16

Class I

Answer 16

high solubility
high permeability

Propranolol

Question 17

Class II

Answer 17

low solubility
high permeability

Ketoprofen

Question 18

Class III

Answer 18

high solubility
low permeability

Ranitidine

Question 19

Class IV

Answer 19

low solubility
low permeability

HCTZ, furosemide

Question 20

IVIVC

Answer 20

predictive mathematical model describing relationship between in vitro property and in vivo response

in vitro rate or extent of drug dissolution or release
to predict
in vivo live plasma drug concentration or amount of drug absorbed

Question 21

diffusion coefficient

Answer 21

D

cm2/sec

Question 22

permeability coefficient

Answer 22

P

cm/sec

Question 23

partition coefficient

Answer 23

K

unitless