The Solid State

Question 1

What is a solid?

Answer 1

A material that retains its shape unless a compression force is applied. Most drugs/excipients are solid at room temperature.

Question 2

What are the two extremes of solid materials?

Answer 2

Amorphous and crystalline

Question 3

What is an amorphous solid?

Answer 3

A materia with no detectable crystal structure/without clearly defined form.

Question 4

Characteristics of an amorphous solid?

Answer 4

• Short range order
• Random, statistical arrangements
• Comparable to liquids, but solid - highly viscous
• Also called glass or supercooled melt

Question 5

What is a crystalline solid?

Answer 5

Arranged in a regular crystal lattice, with ordered arrangement of atoms, ions or molecules.

Question 6

Characteristics of a crystalline molecule?

Answer 6

• Long range order
• 3D periodic arrangement
• Anisotropic physical behaviour e.g. cutting diamond to reflect light

Question 7

What is a polymorph?

Answer 7

One component can take many different forms i.e. different crystal packing

Represents different stages of solid matter.

They will have different properties.

Question 8

What are the varying physico-chemical characteristics that vary between polymorphs? (5)

Answer 8

• Solubility (physical and chemical)
• Melting point
• Density
• Habit
• ## Colour

Question 9

Case study example drug of a polymorph? Key notes?

Answer 9

Drug: Ritonavir - treatment of HIV/AIDS

• Formulated as a crystalline tablet
• During manufacture, a new more stable structure appeared in crystallization - lower solubility, poorer bioavailability
• Patients reported no effect - had to be reformulated - very costly

Question 10

2 types of polymorphs?

Answer 10

1. Packing polymorphism

2. Conformational polymorphism

Question 11

What is packing polymorphism?

Answer 11

Same conformation of molecule but different packing

Question 12

What is conformational polymorphism?

Answer 12

Different conformation of molecule in crystal lattice - likely leading to different packing.

Question 13

What is a phase diagram? Use?

Axis?

Components?

Answer 13

Diagram used to describe regions of existence of different polymorphs - helps in manufacture for generation of different crystal forms.

Usual axis: temperature & pressure

Phase boundaries separate the environments in which certain crystal forms can exist.

Question 14

Which phase rule is used to work out how many different crystal forms are stable in a system at any condition?

Answer 14

Gibbs phase rule

P + F = C + 2

P = number of phases/stable crystal forms 
F = degrees of freedom 
C = number of components 

With polymorphs, C = 1

Question 15

What is a co-crystal?

Answer 15

Crystalline structure composed of at least 2 components (atoms, ions, molecules)

Can form between any two molecules independent of their state of matter i.e. at room temp one is solid, one is gaseous