Lecture 16 - drug solubility and dissolution rate 1

Question 1

Give the organs in the GI tract.

Answer 1

Question 2

Two ways in which an aqueous solution may be absorbed.

Answer 2

• Aqueous solution –> straight into GI fluids –> absorbed
  OR
• Aqueous solution –> precipitation –> suspension of fine particles in GI fluids –> solution of drug in GI fluids –> absorption

Question 3

How does an aqueous suspension get absorbed?

Answer 3

Aqueous suspension –> suspension of fine particles in the GI fluids –> solution of drug in GI fluids –> absorption

Question 4

How do immediate dosage forms get absorbed?

Answer 4

Immediate release dosage from –> aggregates granules –> suspension of fine particles in GI fluids –> absorption

Question 5

Drugs already in solution are absorbed much…

Answer 5

faster

Question 6

Solution

Answer 6

Solution is a molecular dispersion formed by 2 or more components which form a one phase homogenous system

Question 7

Mixture

Answer 7

A mixture of two or more components that forms a single phase which is homogenous down to the molecular level

Question 8

Solvent

Answer 8

the component that determines the phase of the solution is the solvent. The solvent is the largest proportion of the system

Question 9

Solutes

Answer 9

the other components of the solution. Are dispersed as molecules or ions throughout the solvent- dissolved in the solvent

Question 10

Saturated solution

Answer 10

solute is in equilibrium with the solid phase

Question 11

Solubility - in quantitative terms - give two definitions.

Answer 11

the concentration of solute in a saturated solution at a certain temperature. OR The maximum mass or volume of solute that will dissolve in a given mass or volume of solvent at a particular temperature

Question 12

Solubility - qualitative

Answer 12

the spontaneous interaction of two or more substances to form a homogenous molecular dispersion

Question 13

Unsaturated solution

Answer 13

the dissolved solute is in concentration below that necessary for complete saturation at a definite temperature

Question 14

Supersaturated solution

Answer 14

contains more of the dissolved solute that it would normally contain at a definite temperature. Dissolution of large amounts at an elevated temperature. Upon cooling will fail to crystallize from the solution

Question 15

solubility can be expressed in terms of molarity and molality. What does that mean?

Answer 15

Molarity- number of moles of any compound per litre
Molality = number of moles in 1kg of solvent.

Question 16

The BCS classifies drugs according to solubility and permeability. Give the four classes.

Answer 16

Class one- high solubility/high permeability
Class two – low solubility/ high permeability
Class three – high solubility/Low permeability
Class four – high solubility/ high permeability.

Question 17

define dissolution

Answer 17

describes the process by which drug particles dissolve.

Question 18

For a drug to be absorbed it must be….

Answer 18

IN SOLUTION

Question 19

Describe what is going on in this diagram.

Answer 19

1. Diffusion layer: during dissolution the drug molecules in the surface layer dissolve to form a saturated solution around the particles
2. The dissolved drug molecules then pass through the dissolving fluid to contact absorbing mucosa and are absorbed. The drug eventually enters bloodstream.
   The diffusing layer is replenished by further drug dissolution- absorption continues.

Question 20

The rate of dissolution is determined by the slower step. What is the slowest step in dissolution?

Answer 20

The diffusion of the solute from the saturated solution surrounding the drug particle to the bulk of the solution.

Question 21

Give Fick’s law equation and label it, in terms of dissolution.

Answer 21

Question 22

Fick’s law states that the mass transfer of solute molecules through the diffusion layer is directly proportional too…… and inversely proportional to…..

Answer 22

directly proportional to the area available for migration (diffusional surface area) and the change in concentration across the boundary layer.

The rate is inversely proportional to the thickness of diffusion layer

Question 23

Give Noyes-Whitney equation and label it in reference to dissolution.

Answer 23

Question 24

The Noyes-Whitney equation states that dissolution rate can be increased by increasing…

Answer 24

the surface area of the drug by reducing particle size, increasing drug solubility in diffusing layer, Increasing K- dissolution rate constant.

Question 25

Why shouldn’t you crush be tablets and give it to a child?

Answer 25

Increases dissolution rate because the surface area is increased. This can potentially be toxic.

Question 26

K in the Noyes Whitney equation is the diffusion rate constant. How can it be calculated?

Answer 26

D = the diffusion coefficient of the solute in the solvent. V= the volume of the dissolution medium. h= the thickness of the boundary layer.

Question 27

If drug dissolution is fast, the rate of absorption of a drug is dependent upon…?

Answer 27

its ability to pass through the absorbing membrane.

Question 28

If drug dissolution is low, what is the rate limiting step in absorption?

Answer 28

dissolution

Question 29

Name factors affecting the dissolution rate

Answer 29

A -surface area of solid drug particle
Cs- solubility in the dissolution medium
C - concentration in the bulk of the solution at a given time
D - diffusion coefficient of the solute in the solvent
h - thickness of boundary layer

Question 30

What can affect the surface area of solid drug particle?

Answer 30

size of particles
porosity
dispersibility
surfactants

Question 31

What affects solubility in the dissolution medium?

Answer 31

temperature, nature of solvent and solute, pH, crystalline form, presence of other compounds, solubility agents.

Question 32

Reducing particle size will ……………. dissolution rate. Why?

Answer 32

the reduction of particle size increases dissolution rate. This is because there is an exposure of increasing amounts of solute to the solvent.

Question 33

Particle size can effect, what?

Answer 33

stability/less stable - penicillin
side effects - nitrofurantoin

Question 34

How does structure of the solute effect solubility?

Answer 34

• Molecular area, shape, boiling and melting points and functional groups/substituents and their positions can change solubility.
• The use of salt form increases solubility- higher degree of dissociation in water, increased interaction with the solvent, increases solubility.