| Is there a risk for chemical degradation
of the drug substance
in solution? |
□ Yes □ No |
| Is there a risk for physical degradation,
such as |
|
| polymorphic form change |
□ Yes □ No |
| precipitation of crystalline
form from an amorphous state |
□ Yes □ No |
| precipitation of the
free form from salt/cocrystal |
□ Yes □ No |
| other |
□ Yes □ No |
| Is dissolution
incomplete (less than assay value) under sink
conditions? |
□ Yes □ No |
| If yes, an investigation
of the root cause should be provided. |
| Is
the dissolution rate influenced by the presence of certain
excipients (e.g., cyclodextrins, ionic interaction with croscarmellose
sodium)? |
□ Yes □ No |
| If yes, it needs to be
carefully assessed whether the interaction
has any in vivo relevance and whether this effect can be captured
mechanistically in the dissolution model. |
| Is the DS or DP wettability poor in aqueous media? |
□ Yes □ No |
| Is there a risk for interaction with medium components?
(e.g.,
ionic interaction with buffer species or surfactants) |
□ Yes □ No |
| Is sedimentation or coning observed during in vitro dissolution? |
□ Yes □ No |
| Is the solubility at the DS or DP surface expected
to be different
from the bulk solubility? |
□ Yes □ No |
| If yes, the surface solubility should be measured or computed. |
| What is the mechanism of release and is it compatible
with
the erosion of particles from their outside surface? |
□ Yes □ No |
| If yes, the approaches such as Z-Factor
or P-PSD can be applied |
| Is there a delay
to drug release due to capsule opening or
tablet disintegration? |
□ Yes □ No |
| If yes, the
capsule opening/disintegration should be mechanistically
modeled or the time for drug release should be removed from the measured
dissolution time point prior to fitting dissolution. |
