Block 4 -- Diffusion & Dissolution

Question 1

Define diffusion:

Answer 1

mass transfer of individual particles brought about by random molecular motion

Question 2

What factors affect the diffusion coefficient?

Answer 2

1) T
2) Pressure
3) Solvent properties
4) Solute properties

Question 3

Give examples of diffusion coefficients for big and small particles.

Answer 3

Big – 10^-6

Small – 10^-7

Question 4

Define flux:

Answer 4

the amount of material (M) flowing through a cross-section (S) of a barrier in a specified amount of time (t)

Question 5

What does Fick’s First Law show?

Answer 5

The amount of material (M) flowing through a unit barrier in a unit time

Question 6

What does the negative sign in Fick’s first law signify?

Answer 6

Diffusion occurs from higher to lower concentration

Question 7

What does Fick’s Second Law show?

Answer 7

How concentration changes with time at a particular location

Question 8

Describe the diffusion cell:

Answer 8

1) donor compartment
2) receptor compartment
3) Membrane
4) Inflow of solvent to receptor

Question 9

Why would C_1 be greater than C_D?

Answer 9

If the drug is lipophilic and sequesters in the membrane

Question 10

Describe conditions and kinetics at steady state in the diffusion cell?

Answer 10

Zero-order release

Sink conditions

Question 11

How can you find the Permeability coefficient from a graph?

Answer 11

M = PSC_dt
Slope = PSC_d

Question 12

Why is a lag time associated with non-steady-state conditions?

Answer 12

Lag time is present to establish a uniform concentration gradient within membrane

Question 13

Define dissolution rate:

Answer 13

the amount of API in a solid dosage form dissolved per unit time under a set of standardized conditions of liquid/solid interface, T, media composition

Question 14

Why is the dissolution rate tested?

Answer 14

1) To measure quality control in formulation & manufacturing.
2) To ensure bioequivalency when F correlates with dissolution.
3) To establish the intrinsic dissolution rate of drug.
4) To identify “F” problems in preformulation
5) To quantify stability/shelf-life.

Question 15

Describe the in-vivo and in-vitro sink conditions.

Answer 15

In-vitro
   1) large volume of dissolution medium
   2) replenishing medium at specific rate [solute] always < 10-15% of max solubility
in-vivo
   1) GI tract

Question 16

What are the units for D?

Answer 16

cm2/s

Question 17

What are the units for P?

Answer 17

cm/s

Question 18

What are the units for K?

Answer 18

none

Question 19

What are the units for C?

Answer 19

mg/cm3

Question 20

What are the units for t?

Answer 20

s

Question 21

What are the units for V?

Answer 21

mL

Question 22

What are the units for k?

Answer 22

cm/s

Question 23

What are the assumptions for powder dissolution rate calculations?

Answer 23

1) uniformly-sized particles

2) radius of particle does not remain constant (dV=4(pi)r2*dr

Question 24

What is the area of a circle?

Answer 24

4 (pi) r2

Question 25

When is Hixon-Crowell's Cube Root Law not used?

Answer 25

for very small particles

Question 26

What factors affect dissolution rate?

Answer 26

1) solubility 2) wetting 3) particle size 4) crystalline state 5) hydration 6) complexation 7) additives