| Dissolution data on at least 3 independent
methods using the
same batch |
The dissolution conditions should be adapted
to the DS or DP
properties and the intended use of the model. For example, neutral
compounds may require dissolution profiles with a range of doses,
volumes, and presence of surfactants. Ionizable drugs may require
media with different physiologically relevant pH conditions. If the
model is intended to predict food effects, dissolution in FaSSIF and
FeSSIF is helpful, while if the model should predict DDIs with acid
reducing agents, testing in acidic and neutral pH conditions would
be logical. If a dissolution method is discarded, a justification
would be useful. |
| Parameters describing
in vitro dissolution conditions |
| Medium volume |
|
| Medium
composition |
|
| Medium pH |
|
| Temperature |
|
| Apparatus type |
|
| Agitation speed |
|
| Drug
dose |
|
| Drug solubility in the
dissolution medium |
The surface solubility should be
measured or computed. If there
is a rapid phase change, e.g., salt disproportionation to a free base,
the free base surface solubility at the pH of medium and using the
buffers of the medium should be characterized. |
| Parameters describing
dissolution media with surfactants |
| Drug solubility in the blank dissolution medium (without surfactants) |
|
| Concentration of micelles |
|
| Drug affinity to the surfactant system |
Ideally, the apparent drug solubility (Sapp) is measured in the buffer of interest with increasing
surfactant concentrations ([S]) above the critical micelle concentration
(CMC). The slope of the linear portion (Sapp vs [S]) describes the drug affinity to the surfactant system. Some
quantitative structure activity relationship (QSAR) models can be
developed to predict the affinity for specific systems based on literature
data. |
| CMC of the surfactant in the dissolution
medium |
Literature data could be valuable. Care is needed
with regards
to the effect of pH and temperature on the CMC of certain surfactants. |
| Size of the micelles |
Literature data
of the pure surfactant micelles could be useful,
but ideally the micelles size is measured in presence of the drug.
For this purpose, at the end of the dissolution experiment, the medium
is centrifuged, and the supernatant is analyzed using dynamic light
scattering methods. This is important for drugs which have surface
active properties and can form mixed micelles with bile salts or artificial
surfactants. An average hydrodynamic radius is needed. |
