Thermogravimetric analysis and hot stage microscopy

Question 1

What are the two options in solid state characterisation?

Answer 1

1. X ray crystallography

2. Thermal analysis

Question 2

What is thermal analysis?

Answer 2

The study of the effect of temperature on the behaviour of samples such as APIs which are crystalline solids

Question 3

What are the thermal analysis techniques?

Answer 3

1. State changes (melting, boiling)
2. Degradation profiles
3. Complex chemical phenomena

Question 4

What are the different phase transition states and what do they each mean?

Answer 4

1. Melting: transition from solid to liquid due to heat
2. Vaporisation: transition from liquid to gas due to heat
3. Sublimation: Solid to Gas (no liquid phase)
4. Deposition: Gas to solid (no liquid phase)

Question 5

What is desolvation and give an example?

Answer 5

1. Removal of solvent from a material (API) when heat is applied
2. Can occur in liquid or solid
3. Example: Azithromycin dihydrate to Azithromycin monohydate

Question 6

What is the glass transition state?

Answer 6

Transition of amorphous state from hard and brittle state into soft and flexible state under heat application

Question 7

What is decomposition?

Answer 7

The break down of the product into different simpler chemical products from the application of heat

Question 8

What is denaturation?

Answer 8

The disruption and destruction of protein that’s achieved through the increase of heat to the primary and secondary structure

Question 9

What is oxidation?

Answer 9

Applying oxygen to a substance and heating it

Question 10

Describe how hot stage microscopy works?

Answer 10

1. Samples heated through a pre set heating programme
2. Polarisers are used for contrast to visualise the samples properly (especially crystalline material)
3. Can determine phase transition temperatures and crystallisation (not shown in polymorphic materials)

Question 11

Describe what thermogravimetric analysis (TGA) is?

Answer 11

1. Where the sample weight is measured as a function of varying temperature
2. Sample pan in the furnace with a sample of 5 to 20mg
3. Computer measures the loss of mass as temperature increases

Question 12

How do you work out weight change?

Answer 12

[(Starting Weight - Ending weight)/ Ending weight] x 100

Question 13

In thermogravimetric analysis (TGA), what are the processes that can be recorded to show a change in weight and cannot?

Answer 13

Can: 
Vaporisation
Sublimation
Desolvation (important to find solvation)
Decompostion (if you can combust) 

Cannot:
Glass transition
Melting
Decomposition No weight change

Question 14

How can we tell using a desolation graph that a molecule is decomposition rather than evaporation?

Answer 14

Losing over 60% of its mass is thermal decomposition not evaporation

Question 15

What are the instrumental factors that affect the thermogravimetric analysis?

Answer 15

1. Heating rate: quicker heating, gives higher degradation temperature
2. Furnace of atmosphere: Inert atmosphere (high in nitrogen) prevents oxidation
3. Material and geometry of pans (surface area and conductivity)

Question 16

What are the sample factors that affect the thermogravimetric analysis?

Answer 16

1. Mass: small changes in mass may be hard to detect
2. Particle size: increases in surface area as particle size increases
3. Samples pre-treatment: Amorphous vs crystalline- treated before differently
4. Packing: compressed samples may effect thermal conductivity and combustion
5. Thermal conductivity: transfer of heat: has to be even on both sides of the pan

Question 17

How do you apply the findings of TGA?

Answer 17

1. Discover the solvent content
2. Residual solvent
3. Composition of multicomponent systems
4. Thermal stability of materials
5. Oxidative stability of materials
6. Estimated lifetime of product
7. Decomposition of kinetic material