Crystals and Crystallisation 2

Question 1

Describe gas molecules?

Answer 1

1. Randomly orientated
2. Fast moving
3. Large intramolecular/atomic distances

Question 2

Describe Liquid molecules?

Answer 2

1. Randomly orientated
2. Fast moving
3. Smaller intramolecular/atomic distances

Question 3

Describe amorphous solids compared to crystalline solids?

Answer 3

Amorphous
1. Random (short range order)

2. More tightly packed

Crystalline
1. Long range order (Lattice, unit cell)

2. Closely packed structure

Question 4

Explain how you can crystallise a solution from a solid?

Answer 4

1. Dissolve solid in solution
2. Filter the solid and remove it from the solution
3. Allow solution to cool or evaporate the solvent
4. Supersaturated solution (more saturated than it can be)
5. Nucleation and crystal growth (dissolved solid cannot stay in solution- crystals form instead)

Question 5

What does the metastable zone mean?

Answer 5

1. All the way to the supersaturated side of the graph (left)
2. If you drop a crystal onto the solution (seed) when it’s a metastable zone, crystals will form identically to the crystal dropped

Question 6

Describe what happens when a seed is added when a solution is in the metastable zone?

Answer 6

1. Collisions occur between molecules
2. Critical cluster size is formed and further molecules enhance growth
3. Unstable clusters fall apart if not reached

Question 7

When a molecule has a higher amount of intermolecular interactions, what does this mean?

Answer 7

1. More thermodynamically more favourable

2. More tendency for the molecule to leave its solid state and its crystallinity (solubility)

Question 8

In polymorphs, what different physicochemcial properties can change between each one?

Answer 8

1. Solubility in water can change
2. Melting point between each
3. Bioavailability as the polymorph must be soluble in solution which has a direct effect

Question 9

When a molecule is more thermodynamically favourable, what does this mean for the tendency?

Answer 9

Increased tendency for the molecule to leave its solid state and its crystallinity (solubility)

Question 10

What occurs if you change the solvent for each different polymorph?

Answer 10

1. No change
2. The order of solubility stays the same
3. If one is more soluble in one solvent, it’ll be the same in the other

Question 11

If a polymorph is more stable than another, what does this mean?

Answer 11

1. Polymorph is the least soluble

2. Less likely to transform unexpectedly unlike a less stable polymorph

Question 12

What is the solution to correcting a polymorph that is less soluble?

Answer 12

1. Turn it into a salt form of the API

2. Example: Turn it into a Hydrochloride

Question 13

Why are amorphous solids not used for drug production mainly?

Answer 13

1. They have excellent solubility

2. However, they have the tendency to revert to lower solubility crystalline forms

Question 14

Define what characterises crystal structure?

Answer 14

1. Unit cell size and shape

2. Atomic positions