Crystals and crystallisation

Question 1

What are agglomerates of crystals?

Answer 1

The particles that you can see when you look under a powder with a microscope

Question 2

What can you use X-ray diffractometer for?

And describe what is seen?

Answer 2

1. You can use it to see individual molecules that are arranged in regular pattern
2. Material is crystalline and the molecules are not covalently bonded to one another

Question 3

How do you obtain a drug to be absorbed into the blood stream?

Answer 3

The drug has to disintegrate from a tablet into granules, into particles and into a drug in solution.

THEREFORE DRUG HAS TO BE IN SOLUTION.

Question 4

Why do we need to know about the relevance of the solid state in terms of formulation and manufacture?

Answer 4

1. Solid dosage forms widely used (tablets and capsules) due to stability
2. Raw materials (including API) are powders
3. Physicochemical properties of these powders (particle shape) are related to the underlying solid state structure of the material
4. Understanding the solid state structure helps us understand and possibly control physicochemical properties to our advantage- how it reacts in patients

Question 5

What does solubility rely on?

Answer 5

Crystal structure

Question 6

What does dissolution rely on?

Answer 6

Solubility

Question 7

What might bioavailability depend on?

Answer 7

Dissolution rate

Question 8

What’s the difference between solubility and dissolution?

Answer 8

1. Solubility is the max amount that can be dissolved per unit volume
2. Whilst dissolution is a process in which a solid dissolves to form a solution.

Question 9

Describe what long range order means in crystalline material?

Answer 9

Where molecules are arranged in a regular manner in three dimensions over a long range (typically several thousand molecules in each direction)

Question 10

What does it mean to be in a amorphous state?

Answer 10

1. When it’s non-crystalline as there is a lack of long range order of their constituent molecules
2. Molecules are arranged randomly like in a liquid but it’s a solid- example: glass

Question 11

Name and describe the four non covalent intermolecular forces?

Answer 11

1. Electrostatic interaction that’s strong, occurs between ions
   Example: NH3+—-Cl-
2. Hydrogen bond that’s intermediate strength and occurs between two permanent dipoles
   Example: C=O —– H-O
3. Dipole Dipole interaction that’s weak and arising from permanent dipoles
   Example: C-H———F
4. Dispersion that occurs between all molecules which as a weak, arising from transient dipoles
5. Three and four are known as van der waal forces

Question 12

Describe a crystal unit cell?

Answer 12

1. Crystal is three dimensional, so we also need the z direction.
2. There are no gaps between unit cells
3. The unit cell does not have to be shaped like a regular brick (though it might be)
4. The unit cell contains atoms in particular places

Question 13

What are polymorphs?

Answer 13

The different three dimensional packing arrangements of the same object
Example: different crystal structures

Question 14

In polymorphs what normally differs?

Answer 14

1. Size and shape of their unit cells

2. Location of the molecule inside their unit cells

Question 15

What properties do famotidine polymorphs have?

Answer 15

Different physicochemical properties including solubility and dissolution

Question 16

What happens when a polymorph is completely dissolved?

Answer 16

Identity is lost and the drug is simply in solution