Lecture 5

Question 1

What form does he drug have to be in to be absorbed ?

Answer 1

Only drugs that are single molecular entities in solution can be absorbed.

Question 2

What is a solution ?

Answer 2

A mixture of two or more components that form a single, molecularly homogenous phase, which is formed by dissolution.

Question 3

What is dissolution ?

Answer 3

The process by which a solid dissolves in a solvent to produce a solution.
The transfer of molecules or ions from a solid state into solution.
Tablets are ground into powder and then the particles are separated into crystals into individual drug molecules.

Question 4

What is faster acting, oral solutions or solids ?

Answer 4

Oral solutions are faster acting than solids.

Question 5

Only drugs in solution can…

Answer 5

… cross the intestinal wall and is absorbed into the systemic circulation.

Question 6

When tablets are first swallowed, they have a relatively small SA, so…

Answer 6

… the amount of solvent that is in contact with the tablet is small.
This means that the dissolution rate is relatively small, i.e. the rate at which the crystals break off and then the molecules break off.

Question 7

What is disintegration ?

Answer 7

The process by which tablets break down into granule.
Tablets are designed to break down rapidly.
The particle size is decreased so the SA is increased resulting in a higher dissolution rate.

Question 8

What is deaggregation ?

Answer 8

The process by which the granules break down into fine particles.
This process increases the SA hugely therefore allowing more contact with the solvent which results in a much faster dissolution rate.

Question 9

Why is it preferred that the break down of the tablet is quick ?

Answer 9

So that the dissolution rate is also quick.

Question 10

What would happen if there is a need for a slow release ?

Answer 10

The tablet needs to be intact for longer and so it takes longer for the tablet to break down for a slower and more sustained drug release.

Question 11

The formulation of the tablet can be used to…

Answer 11

… affect the performance of various drug products.

Question 12

What happens when the drugs are in solution ?

Answer 12

They are available for absorption in the small intestine and can then enter the bloodstream.

Question 13

What is meant by the solubility of a substance ?

Answer 13

The amount of that substance that goes into a solution when equilibrium is established between the solute in solution and the excess (undissolved) substance, i.e. when no more material an be dissolved into the solution - this is the maximum solubility.

Question 14

What is the diffusion layer ?

Answer 14

The layer of solvent that associates around the drug particle.
It is the barrier to the molecule diffusing into the bulk solvent.

Question 15

What will happen to the individual molecules that break off from the crystals ?

Answer 15

They will defuse across the diffusion layer where they enter the bulk solution and into the GI membrane then reaching the systemic circulation.

Question 16

Why do the molecules circulate the body ?

Answer 16

In order to try and find their targets so that they can act within the body.

Question 17

What is the Noyes - Whitney equation ?

Answer 17

It describes the dissolution of drugs in terms of rate and predicts the rate of dissolution.
This equation helps to show how experimental changes can affect dissolution rates.

Question 18

What is meant by the saturate solubility ?

Answer 18

It is the saturated concentration at the surface of solid particle within the diffusion layer.

Question 19

What does the dissolution process rely on ?

Answer 19

It relies on the concentration gradient (differences in concentration) to drive the process.
The whole system is trying to drive towards an equilibrium.

Question 20

The dissolution process - step 1

Answer 20

The molecule leaves the solid particle.

Question 21

The dissolution process - step 2

Answer 21

The molecule diffuses across the diffusion layer.
This is the rate determining step - it is not possible to absorb a drug faster than getting it into solution.
From the start of the molecule’s diffusion, it starts at high concentration but when it reaches the bulk, the concentration much lower - this difference concentration is what drives this process as it is trying to reach an equilibrium in concentration.

Question 22

The dissolution process - step 3

Answer 22

The molecule leaves the diffusion layer and enters the (well-stirred) bulk phase.
This will continue to maintain a low concentration.

Question 23

Factors that affect dissolution rates of solids in liquids

Answer 23

The size of solid particles, the solubility in dissolution media, the volume of dissolution medium, the dissolution medium, the degree of agitation.

Question 24

Size of solid particles

Answer 24

If the total SA increases the particle size reduces.

More porous particles as they have bigger SA so there is more contact.

Question 25

Solubility in dissolution media

Answer 25

Temperature as there is more energy available.

Question 26

Volume of dissolution medium

Answer 26

If there is more solvent in the bulk, the maintained concentration is lower.
If there is less solvent in the bulk then the equilibrium is reached fast and so the dissolution process stops faster.

Question 27

Dissolution medium

Answer 27

How easily the molecules move across the diffusion layer.

The more viscous dissolution medias make it harder for the molecule to defuse across it.

Question 28

Degree of agitation

Answer 28

e.g. stirring, as you stir, there is a reduction in the thickness of the diffusion layer making the dissolution rate faster.

Question 29

Physiological factors affecting drug dissolution

Answer 29

Stomach contents - food components, pH, buffer capacity.
GI motility - transit/emptying rates of the stomach into the small intestines, GI secretions e.g. bile salts, co-administered fluids.

Question 30

What does the Noyes - Whitney equation demonstrate ?

Answer 30

The rate of dissolution from the GI tract ad other sites is limited by the rate of dissolution.

Question 31

What is the rate determining step ?

Answer 31

The dissolution from the solid particle - you cannot absorb drugs faster than you can get the drugs into solution.

Question 32

Key factors that impact a drugs ability to get into solution

Answer 32

Particle size, solubility of the molecule.

Question 33

Why is there a range of substances where there is pharmacopeial control over the particle size ?

Answer 33

Because the particle size affects the dissolution performance.
This allows for there to be predictable properties when reproduced.