Lecture 6: amorphous solid dispersion

Question 1

What are the various BCS classes and what do they mean?

Answer 1

BCS Class:
1 - high solubility high permeability
2 - low solubility high permeability
3 - high solubiltiy low permeability
4 - low solubility low permeability

Question 2

Is amoprhous solid more stable than crystalline?

Answer 2

No

Question 3

Amorphous vs crystalline:
Which has the higher apparent solubility?

Answer 3

Amorphous

Question 4

Amorphous vs crystalline:
Which has the faster dissolution rate?

Answer 4

Amorphous

Question 5

What is an amorphous solid dispersion?

Answer 5

It is a system where the drug is dispersed in a carrier matrix in an amoprhous state. It is used to enhance the solubility & bioavailability of poorly water soluble drugs

Question 6

What is a suitable Tg for a polymeric carrier in an ASD?

Answer 6

Tg should be between 50-180C
The Tg of the API and the carrier should be close to each other, otherwise it can cause phase separation.

Question 7

What is a suitable solubility for a polymeric carrier in an ASD?

Answer 7

Close to that of the API, so avoid phase separation

Question 8

Why is it important for the polymeric carrier in an ASD to have low hygroscopicity?

Answer 8

To prevent nucelation and recrytsallisation

Question 9

What are the different phases an ASD can have?

Answer 9

1. One phase: API is soluble in melted polymer, and is molecularly dispersed in the polymer
2. Two phase: Amorphous API and polymer are immiscible

Question 10

In a one phase ASD, what is the Tg of the API and the polymer?

Answer 10

The phase has 1 Tg

Question 11

In a two phase ASD, what is the Tg of the API and the polymer?

Answer 11

Two glass transition temperatures, one for each component

Question 12

How do you use PXRD to evaluate the drug polymer interaction in an ASD?

Answer 12

Sharp peaks indicate the structure became crystalline not amorphous, so there is a stability issue
Eg: your ASD preparation isnt successful so the drug is still crystalline OR
The ASD preparation was successful but it wasnt stable and because crystalline again

Question 13

What are the characteristics of a suitable polymer for ASD?

Answer 13

1. Immobilize amorphous API
2. Prevents nucleation
3. Protects from moisture
4. Maintains supersaturation
5. Maintains/Reduces Tg
6. Polymer-Drug Interaction

Question 14

Why might reducing Tg be a good thing in ASD?

Answer 14

If you have a very high Tg, it means the API is too hard, so reducing the Tg makes it more flexible which is desirable