Chemistry Reference
In-Depth Information
Figure 3.1.
Solid form screening strategy including amorphous solid dispersions.
miscibility. Early formulations will be relatively straightforward with drug in a capsule or
simpli
ed oral formulations. Later in development, other parameters will be investigated
to determine long-term formulatability, shelf life, and performance. So, a different screen
may be needed to collect this type of information and assess risk management.
There are a number of steps that need to be considered for an amorphous dispersion
screen. These include experimental variables, characterization and property assessment,
and
finally selection.
3.2 AMORPHOUS DISPERSION SCREENING
3.2.1 API and Polymer Properties
Before starting an amorphous dispersion screen
project, information on the active pharmaceutical ingredient (API) is needed. This may
include chemical structure, solid form, physical stability, chemical stability, log
P
,
hydrogen bond donors/acceptors, calculated solubility parameters, and known solubili-
ties of the solid in various solvents/biorelevant media. In early development, only some
of these properties will be known and it will be necessary to obtain additional data as
needed to move forward.
Solid-state characterization of the initial API as received is the
3.2.1.1 API Characterization
rst step and can
include techniques summarized in Table 3.1 that would determine properties such as
crystallinity/form, thermal properties, volatile content, and water uptake. This initial set
of data will establish a baseline for later comparison with amorphous solid dispersions
prepared during the screen.
