Physical stability

What is physical stability?

- The changes in the physical properties of the product in the absence of chemical changes to the drug.

- Changes can occur to active ingredients as well.

What can changes in physical stability affect?

The effectiveness, dosing and appearance of the product.

What are the possible changes in tablets?

- Disintegration time.

- Dissolution rate.

- Hardness and appearances.

What are the possible causes of physical changes of tablets?

- Changes in drug polymorphic or solvate form.

- Changes in physical properties of excipients.

- Moisture uptake

- Cracking and chipping

How can you test the parameters of tablets?

Measuring:

- Dissolution

- Water content

- Hardness

What are the possible changes of capsules?

- Dissolution rate

- Appearance

- Strength

What are the possible causes of physical changes of capsules?

- Aggregation of powders.

- Property changes of capsule shell.

- Changes in drug physical properties.

How can you test the parameters of HG capsules?

Measuring:

- Brittleness

- Dissolution

- Microbial contamination

How can you test the parameters of SG capsules?

Measuring:

- Dissolution

- Microbial contamination

- Leakage

What are the possible changes of solutions?

Flavour, discolouration, precipitation

What are the possible causes of physical changes of solutions?

- Drug crystallisation

- Inadequate excipients

- Interaction with packaging

How can you test the parameters of solutions?

Measuring:

- Precipitation

- Viscosity

- pH

How can you test the parameters of parenteral solutions?

Measuring:

- Colour

- Sterility

- Endotoxins

What are the possible changes of suspensions?

- Sedimentation

- Crystal growth

What are the possible causes of physical changes of suspensions?

- Changes in particle size.

- Inadequate excipient

- Changes in pH

How can you test the parameters of suspensions?

Measuring:

- Precipitation

- pH

- Viscosity

- Microbial contamination

What are the possible of physical changes of solutions?

- Changes in droplet size.

- Drug crystallisation or aggregations.

- Inadequate excipients.

What are the possible changes of emulsions?

Coalescence, Phase separation

How can you test the parameters of emulsions?

Measuring:

- Phase separation

- pH

- Viscosity

What is doseability?

Taking samples at the top, middle and bottom of the bottle.

What is flocculation?

When particles come together to form larger aggregates.

What are the possible changes of semi-solids?

- Drug release rate

- Texture

- Appearance

What are the possible causes of physical changes of semi-solids?

- Changes in drug solid form.

- Particle size change

- Physical instability of base material.

How can you test the parameters of topical semi-solids?

Measuring:

- Clarity

- pH

- Homogeneity

How can you test the parameters of semi-solids (suppositories)?

Measuring softening/melting temperature change.

Should melt at body temp but remain firm under ordinary storage conditions.

Describe stress testing.

- Assessment of susceptibility of drug to degradation at pre-formulation stage.

- Higher stress is applied than normal but only short term

- Used to inform formulation design and explore drug sensitivity.

What is required to conduct a stability study?

- Develop assays for stability.

- Follow ICH guidelines for storage conditions and times.

- Interpret stability data.