Chemistry Reference
In-Depth Information
Is API
thermally
stable?
Y
N
Is API
solubility in
organic
solvent
>5%
Spray congealing,
coprecipitation,
etc.
Is API
T
m
<
225 °C
No
Yes
Yes
Is API
solubility in
organic
solvent
>5%
Yes
Solvent
method
Soluble in low-
melting solvent
Soluble in
volatile solvent
No
Yes
HME
(fusion)
Spray
drying
Freeze
drying
Figure 11.1.
Decision tree for the selection of process for solid dispersion.
generally not compressible enough for tableting. Spray drying, meanwhile, is versatile
(although the spray-dried material may need to be rendered more
flowable and
compressible before tableting, as described above). However, SDDs often function
poorly in capsule form; in fact, they might not be released at all. When a capsule is
immersed in an aqueous environment (for instance, the stomach), a small amount of
uid
penetrates the capsule and begins to dissolve it. With an SDD, this
fluid can mingle with
the polymer present in the dispersion, cross-linking individual polymer molecules and
creating a thick gel that entraps the API and prevents it from being released [29,30].
The considerations described above are summarized below in a decision tree
(Figure 11.1). Ultimately, as this
ects, the choice of amorphization technique
is a multifactorial decision, and no one technique is right for every compound or every
development program. Regardless, once a development group has chosen its approach,
the project enters a distinct new phase
gure re
one that should be guided, at every step, by the
paradigm of QbD. The next section brie
—
y describes the strategic rami
cations of
running a development program under QbD. Subsequent sections speci
cally address
the processing, methods, and stability considerations of an actual program, the develop-
ment of our
first drug commercialized in-house, telaprevir.
