L16 - Drug Solubility And Dissolution Rate 1

Question 1

Why should a pharmacist understan solubility and dissoluiton rate?

Answer 1

• most drugs function in solution in the body
• poorly soluble compounds tend to be eliminated from the GI tract before dissolution

Question 2

Why must drugs dissolve before being absorbed?

Answer 2

• need to determine the rate and extent of absorption (bioavailability)
• low aq ability -> frequent BA problems (poor)

Question 3

What is the definition of a solution?

Answer 3

• mixture of 2 or more components that forms a single phase which is homogenous down to the molecular level

Question 4

What can the definition of solution apply to?

Answer 4

Solid, liquid, and gaseous state
- miscibility

Question 5

What is the definition of a solvent?

Answer 5

The component that determines the phase of the solution
- usually constitutes the largest proportion of the system

Question 6

What is the definition of solutes?

Answer 6

The other components of the solution
- dispersed as molecules or ions throughout the solvent

Question 7

What is the definition of a saturated solution?

Answer 7

Solute is in equilibrium with the solid phase (solute)

Question 8

What is the definition os solubility (in quantitative terms)?

Answer 8

The conc of solute in a satureated solution at a certain temp

• max mass/vol of solute that will dissolve in a given mass/vol of solvent at a particular temp

Question 9

What is the definition of solubility (in qualitative terms)?

Answer 9

The spontaneous interaction of 2 or more substances to form a homogenous molecular dispersion

Question 10

What is the definition of an unsatureated/subsaturated solution?

Answer 10

The dissolved solute is in conc below that necessay for complete saturation at a definite temp

Question 11

What is the definition of a supersaturated solution?

Answer 11

Contains more of the dissolved solute that it would normally contain at a definite temp

Question 12

What does the biopharmaceutical classification scheme (BCS) classify drugs according to?

Answer 12

• their solubility across the intestinal pH range
• their permeability across the GI mucosa

Question 13

What does the BCS’s classification od drugs help with?

Answer 13

• predicts bioavailability issues
• helps to design relevant in vitro dissolution tests

Question 14

What is a disperse system?

Answer 14

Emulsions and suspensions
- 0.1 mcm: 2 phases

Question 15

What is a colloidal dispersion?

Answer 15

2 phases

Question 16

What are solutions of macromolecular material?

Answer 16

Polymer material

Question 17

What are association colloids?

Answer 17

Micelles

Question 18

What are microemulsions?

Answer 18

1 phase, isotropic
- both homogenous and heterogenous
- 1nm to 1mcm

Question 19

What must a drug do first in order to be absorbed?

Answer 19

Be dissolved in the fluid at the site of absorption

Question 20

What does dissolution describe?

Answer 20

The process by which the drup particles dissolve

Question 21

What is the diffusion layer?

Answer 21

The drug molecules in the surface layer dissolve to form a saturated solution around the particles

Question 22

What must the dissolved drug molecules pass throughout?

Answer 22

The dissolving fluid to contact absorbing mucose and are absorbed

Question 23

How does absorption continue?

Answer 23

Replenishment of diffusing layer by further drug dissolution

Question 24

What are the 3 steps in the dissolution rate?

Answer 24

I. molecules of solid solute become molecules of solid in solvent
II. solution in contact with the solid becomes saturated
III. solute molecules migrate through the diffusion layer

Question 25

What is the dissolution rate determined by?

Answer 25

The slower step (III)

Question 26

What is the rate of dissolution determined by?

Answer 26

The diffusion of solute through the static boundary layer

Question 27

What is the rate of mass transfer of solute molecues (or ions) through a diffusion layer…?

Answer 27

• directly proportional to the area available for migration and the deltaC across the boundary layer
• inversely propotional to the thickness of the diffusion layer

Question 28

What can dissolution rate br raised by?

Answer 28

• increase SA by reducing size particle
• increase drug solubility in diffusing layer
• increase k

Question 29

What dimensions does k have?

Answer 29

Length^-2
Time^-1

Question 30

If dissolution fast/ or drug deliver remained in solution what happens to rate of absorption?

Answer 30

Rate of absorption is primarily dependent upon its ability to traverse the absorbing membrane

Question 31

If drug dissolution slow (physicochem properties/formulation factors), what may dissolution be?

Answer 31

The rate limiting step in absorption
- influencing drug bioavailability

Question 32

What does a reduction in particle size do to the dissolution rate and how?

Answer 32

Increases dissolution rate
- exposure of increasing amounts of solute to the solvent

Question 33

What factors should be considered when reducing particle size?

Answer 33

• stability
• aggregation

Question 34

What is the influence of temperature in dissolution rate?

Answer 34

• dissociation in water = endothermic
• dissolution = exothermic

Question 35

What can small changes in the molecular structure of a solute change?

Answer 35

Its solubility in the solvent

Question 36

How does structure of the solute influence?

Answer 36

• use salt form to increase solubility
• reduce aq solubility

Question 37

What is the reduction of aq solubility suitable for?

Answer 37

• masks the taste
• protect from degradation in GI
• facilitates absorption from GI tract

Question 38

Why use a salt form of a drug instead of a the free acid?

Answer 38

• sodium salt has a higher degree of dissociation in water
• increased interaction with solvent
  = increased solubility

Question 39

What are the %s for polymorphism?

Answer 39

• 63% of barbiturates
• 67% of steroids
• 40% of sulphonamides