Amorphous Systems

Question 1

What is an amorphous material?

Answer 1

Materials with no long range structure (no regular repeating units)

Question 2

What is the key temperature?

Answer 2

Glass transition Tg - measured by thermal methods - dsc

Question 3

What is an amorphous material like below Tg?

Answer 3

Hard and brittle - low mobility

Question 4

What is an amorphous material like above Tg?

Answer 4

Soft - high mobility

At higher temps it will flow and become liquid

Question 5

What effect does water have on amorphous materials?

Answer 5

Acts as a plasticiser - lowers Tg

Question 6

Lack of crystalline lattice means….

Answer 6

Dissolution is faster as the lattice doesn’t have to be broken down - higher solubility than crystalline form at same temp

Question 7

What form is best for manufacture?

Answer 7

Amorphous

Question 8

Polymers have long chains that are so large it is difficult for them to….

Answer 8

Arrange themselves to form a crystal - they tend to have high Tg values

Question 9

Most drugs are….

Answer 9

Smaller molecules that can easily form regular repeating structures.

Question 10

What is the natural thermodynamicakky stable form for drugs?

Answer 10

Crystalline

Question 11

How do you create an amorphous material?

Answer 11

1. Melted material that is cooled too quickly to allow molecules to orientate to form crystal nuclei
2. Solutions that are dehydrated quickly
3. Solids that are subject to high energy processes that break the crystalline lattice

Question 12

Creation of amorphous materials is known as….

Answer 12

Amorphization

Question 13

What are unintentional means of amorphization?

Answer 13

1. Dehydration
2. Compaction
3. Size reduction

Question 14

Why is unintentional more problematic that intentional?

Answer 14

1. Mixed systems
2. Regulatory

Question 15

What are the intentional means of production?

Answer 15

1. Spray drying produces fine reducible powder
2. Smashing apart crystalline lattice with steel balls

Question 16

What does the absence of a crystal lattice provide?

Answer 16

Lower energy barrier to dissolution compared to crystalline

Question 17

How do you stabilise amorphous drugs?

Answer 17

Co-amorphous systems (co-formers)

Question 18

What are the general considerations for coformer selection?

Answer 18

1. Diff in pKa
2. H2 binding potential
3. Miscibility
4. Crystallisation behaviour
5. Tg

Question 19

If the coformer is another API…

Answer 19

1. Pharmacological requirements
2. Regulatory constraints
3. Main criterion is the beneficial therapeutic effect arising from co-administration of both substances

Question 20

What is the mechanism of stabilisation?

Answer 20

1. Molecular mobility - increasing Tg
2. Anti-plasticisation effect - increases Tg
3. Specific interactions such as heterodimer formation
4. One component in excess acts as crystallisation inhibitor

Question 21

How does a solid dispersion work?

Answer 21

Similar to liquid dispersions

Drug is dispersed within a polymer that acts as a solvent

System has structure of a liquid dispersion but mobility of a solid