The Solid State

Question 1

Why are solids important In the pharmaceutical sector? (2)

Answer 1

• many medicines are in solid dosage form

- solid properties affect the importance of medicines by dictating key performance parameters like solubility

Question 2

What happens with Norvir?

Answer 2

It was a drug which failed the dissolution test due to the solid form due to formation of crystals which affected its dissolution.

contains Ritonavir

Question 3

Solid properties (3)

Answer 3

rigid structure

resist changes to shape and volume

physical state of matter

Question 4

Types of solid forms: (2)

Answer 4

Crystalline - order of the arrangement is the same throughout the whole structure

Amorphous - order of the arrangement of molecule differs through the structure.

Question 5

Crystalline solid facts (4)

Answer 5

made up for repeating units

defined geometric shape

sharp melting point

have long and short-range order

Question 6

Amorphous solid facts (4)

Answer 6

no sharp melting point but have a glass transition temperature (transition to semi-solid)

irregular molecule arrangement

thermodynamically less stable than crystals

only have short-range order

Question 7

How does a X-ray diffraction shows us if a solid is crystalline or amorphous?

Answer 7

crystalline - distinct sharp peaks

amorphous - broad trace with no distinct sharp peaks

Question 8

Polymorphism is..

This is possible because..

Answer 8

when crystalline solids can take many different shapes/arrangements

this is possible because of multiple functional groups

Question 9

Polymorphism doesn’t affect…

Answer 9

intrinsic properties
e.g. molecular weight/ pKa

These will be the same no matter the arrangement.

Question 10

Examples of polymorphism

Answer 10

Graphite is a polymorphic compound of Diamond.

Question 11

What is Transformation?

Answer 11

One solid form can spontaneously convert to another depending on favourable environmental conditions.

Question 12

Most stable and least stable solid structure?

Answer 12

Most - crystalline

Least - amorphous

Question 13

Most soluble and least soluble solid structure?

Answer 13

Most - amorphous

Least - crystalline

Question 14

Stability depends on…

Answer 14

environmental conditions

Question 15

The greater the stability, the lower the…

Answer 15

solubility

Question 16

An example of a drug who presents polymorphism:

Answer 16

Paracetamol
Form 1
stable, easy to crystallise but hard to compact

Form 2
metastable, difficult to crystallise but easy to compact

Question 17

What happens with the forms of Chloramphenicol?

Answer 17

mixture of alpha and beta crystals where b form is more water soluble and has greater oral bioavailability.

the more beta = absorbed quickly and more effective.

Question 18

What happens to the Ritonavir in the capsule?

Answer 18

A new crystal type has been formed - different arrangement that they had never seen.

Question 19

Properties that vary between polymorphic forms: (4)

Answer 19

density

melting point

solubility

compatibility