Preformulation

Question 1

What are the characteristics evaluated during preformulation studies? What is the importance of evaluating these characteristics?

Answer 1

spectroscopy – IR, UV – identification

solubility – what will It dissolve in, how will it delivered
= (most are solid dosage form e.g. tablets, capsules which will have to be dissolved in the GIT in order to be absorbed and exert a therapeutic effect)

thermal analysis – melting point can be grouped by the term ‘thermal analysis’
= used to determine dissolution in the GIT

powder flow – implications for powder flow

compression properties – important as most drug substances are formulated as tablets which need to be compressed

excipient compatibility – checks if it will sit with excipients well
= will not decompose, etc - reducing sugars act on primary and secondary amines so cannot be used together

Question 2

What is thermal analysis?

Answer 2

measurement of a property of sample
- as the sample is subjected to a controlled temperature programme

temperature programme

• constant heating/cooling
• a constant temperature – isothermal
• modulated or stepped

Question 3

Why is thermal analysis important? What can it be used to find?

Answer 3

degree of crystallinity
crystal purity
solubility
polymorphs/solvates (pseudo-polymorphism)
degradation of components
drug-excipient or excipient-excipient interaction

Question 4

What are the different parts of a TGA?

Answer 4

Thermogravimetric Analysis

microbalance
sample holder - holds 10-20 mg of material
furnace - is raised to surround the sample

thermocouple – hangs next to the sample holder
= takes information about the air within the furnace and feeds back to the TGA so the TGA can control the temperature the sample is exposed to

Question 5

How does a power compensation DSC work?

Answer 5

heat up sample in a platinum pan along with a reference pan at the same rate

temperature rate is controlled by individual sensors that feedback into individual heaters

the power required to heat up 1 pan is subtracted from the other to give a direct measure of the power required to heat the sample and allow it to undergo any events

Question 6

What is a DSC?

Answer 6

Differential Scanning Calorimetry

- looks at the power difference between sample and reference

Question 7

What are pharmaceutical applications of differential scanning calorimetry?

Answer 7

sample identification
sample purity
determination of melting point
detection of polymorphism
detection of crystallinity/amorphicity
measurement of glass transitions
determination of heat capacity
drug-excipient (in)compatibility

Question 8

What happens if a fast scan rate is used in DSC?

Answer 8

glass transition might be larger

recrystallization event might disappear

you could measure the the melt directly without interference of the recrystallisation

Question 9

What occurs in DSC? (order of events)

Answer 9

typically

• heat capacity (flat)
• glass transition (flat) = glass (brittle) to rubber/becomes more mobile
• recrystallisation (peak)
• melt (peak)

melt goes in the direction of endothermic events
(endo up = melt up)

melt/recrystallisation are opposite (peaks in different directions)

Question 10

What is polymorphism?

Answer 10

polymorphism – different organisations of the same molecule = can have different melting points