Chemistry Reference
In-Depth Information
Figure 3.7.
Amorphous dispersion decision tree. (Reproduced with permission from
Ref. 4. Copyright 2010, Wiley.)
the rest are moved to the next decision point. An example of a decision tree for an
amorphous solid dispersion is given in Figure 3.7. The decision points can be grouped
based on various properties, such as physical properties, stability/processing, and
performance. In this example, the
first decision point is obtaining a material that is
amorphous; any materials showing crystalline peaks would not move forward. The
second decision point is acceptable physical characteristics, such as
T
g
, solvent content,
and hygroscopicity. The next is an estimated solubility that is acceptable for develop-
ment. Stability and processing are assessed next and
finally performance. Performance
can be any number of parameters ranging from dissolution rate, lack of crystallization
upon dissolution, to bioavailability. Additional decision points can be added depending
on the development needs and issues. For some companies, solubility and dissolution
may be more important than
T
g
because the material can easily be stored at reduced
temperatures for early studies. Decision points can be moved as needed to
t the
development plan of the molecule.
A form matrix can also be used to identify materials with the most acceptable
properties for development. The materials and selected properties are put into a table and
the acceptable properties are highlighted. The dispersion with the best properties is then
selected for development. As with the decision tree, it is important to understand which
properties should be included for the best selection and these properties may be different
for an early versus late development program. The properties listed in the matrix table
will be speci
c to the system and the development plan. An example is given in Table 3.3
for AMG 517 amorphous solid dispersions [37]. Dispersions containing two polymers at
two drug loadings were prepared by spray drying. A variety of properties were evaluated
for the dispersions, including amorphous nature by XRPD, total volatile content,
T
g
,
