Materials

Question 1

What is bioavailability?

Answer 1

The percentage of a drug that reaches the blood circulation and therefore has an effect.

E.G. 20% Bioavailability = 20% of the drug has an effect / 80% DOES NOT

Question 2

Do crystalline materials or amorphous materials have a long range order ?

Answer 2

Crystalline materials

Question 3

What are the properties of crystalline materials ?

Answer 3

• Long range order
• Predictable
• Have a fixed melting point

Question 4

What are the properties of an amorphous material ?

Answer 4

• No long range order
• May have a non-random pattern / short range order
• Have a glass transition temperature => melts over a long range of temperature
• Less stable than crystal.

Question 5

What is polymorphism ?

Answer 5

When a chemical compound has multiple CRYSTAL STRUCTURES and therefore each has different melting points and solubilities.

This also means that polymorph A will be more stable in a certain temp and pressure range whereas polymorph B will be more stable outside of that range.

However, the solution/melt is the exact same as the rest.

Question 6

Which polymorph is the most stable. The one with the lowest or highest free energy [G] ?

Answer 6

The polymorph with lowest free energy is the stable one

Question 7

What is a monotropic relationship ?

Answer 7

This is when out of two polymorphs, one is ALWAYS the stable one regardless of change in temperature or pressure.

Question 8

What is the opposite of a monotropic relationship ?

Answer 8

Enantiotropic relationship

Question 9

Does a monotropic system have a transition point ?

Answer 9

A monotropic relationship establishes that only one of the polymorphs will remain the most stable regardless of change in temperature.

Ergo this means what the two lines never cross as there is never a point that polymorph B (for example) becomes more stable than that of A.

=> NO, only an enantiotropic system has a transition point

Transition points are also known as critical temperatures

Question 10

Polymorph A has a lower melting point than that of B. Which one is more stable ?

Answer 10

Polymorph B is more stable as it nears the melting point.
It is not a given that it is the more STABLE polymorph throughout all temperatures ranges if we do not know the relationship.

Question 11

What is a critical temperature [T_c]?

Answer 11

A critical temperature is the point in which the stability of polymorph intersects/crosses with another.

Question 12

What is an enantiotropic system ?

Answer 12

It is when all polymorphs are STABLE at different respective temperatures.

Question 13

What is a metastable form?

Answer 13

A form which is thermodynamically unstable but can easily transform to a low energy and STABLE form.

Question 14

What is supersaturation ?

Answer 14

Supersaturation is the process in which a saturated solution is…
* Heated
* More solute is added
* Cooled gently
​
This is the most common way to undergo crystallisation.

Question 15

What are the steps to crystal formation ?

Answer 15

Firstly, a solution undergoes supersaturation in which it cooled down gently.

Followed by the nucleation of the solute molecules when they assemble and reach a critical size.

Question 16

What is nucleation ?

Answer 16

Nucleation is…
* Activation energy is reached for particles to move.
* Aggregation of solute particles in a supersaturated solution occurs.
* Gibbs free energy needs to cross the activation barrier.
* Crystallisation occurs.
* Subsequently, free energy increases as the crystal & nuclei grow.

Question 17

What is a habit of a crystal?

Answer 17

The habit refers to the geometrical shape of a crystal.
These include:
* Tabular
* Platy
* Prismatic
* Acicular

Question 18

Why and how does the habit of a crystal vary?

Answer 18

The habit of crystals vary due to the changes in crystal growth conditions.

For example if there is a increase in the degree of supersaturation it will result in a long, thin needle habit.

The internal arrangement of molecules remains the same.

Question 19

What is a polymoprh?

Answer 19

The specific internal arrangement of molecules in the crystal.

Question 20

How are amorphous materials formed?

Answer 20

Rapid cooling of the liquid or melt will disrupt any crystallisation from occuring.

Question 21

What are the benefits of using amorphous materials in drugs?

Answer 21

They have rapid dissolution which results in a much higher bioavailability.

Question 22

What are the problems surrounding the use of amorphous systems?

Answer 22

They will eventually re-crystallise which is undesirable for a drug.

You want a drug to be stable.

Question 23

What is a hydrate?

Answer 23

A solvate where the solvent is water.

Question 24

What is a solvate?

Answer 24

A crystalline material that contains one or more molecules of the solvent as part of the unit cell struture.

Question 25

What is an anhydrous material?

Answer 25

Describes the absolute absence of water of crystallization.

Question 26

What is water of crystallization?

Answer 26

Water that is chemically bonded into a crystal structure.

Question 27

TRUE OR FALSE

The hydrate forms of an API tend to have a HIGHER solubility than the crystalline non-hydrate form.

Answer 27

FALSE

Question 28

TRUE OR FALSE

The amorphous form of an API has a more RAPID DISSOLUTION compared to the crystalline form of the API.

Answer 28

TRUE

Question 29

Explain dm/dt=DA(Cs-C)/h

Answer 29

• dm/dt is the dissolution rate
• D is the diffusion coefficient
• A is the surface area
• C_s is the solubility
• h is the diffusion layer thickness

Question 30

What is the drug dissolution equation ?

Answer 30

dm/dt=DA(C_s-C)/h