Chemistry Reference
In-Depth Information
removed readily to trap the amorphous API, such as those commonly used in spray
drying. Adequate solubility of both the API and polymer is needed in the solvents chosen
for the screen. Solvent solubilities of common polymers are given in Chapter 14.
Melt experiments do not use solvent and processing must be performed at
temperatures above the
T
g
of the polymer and high enough for the API to either
melt and/or dissolve into the polymer matrix. When using melt experiments, it is
important to ascertain the extent of chemical instability of the drug at elevated
temperatures. For many large-scale extrusion processes, a surfactant may also be needed
and this is considered in a separate section.
T
HERMAL
D
ATA
The melting point and glass transition ratio,
T
m
/
T
g
, can be
combined with the log
P
information to estimate the propensity for crystallization
and drug loading in the dispersion (Figure 3.2); this
figure is based on the use of
HPMCAS only [6]. By plotting log
P
versus
T
m
/
T
g
, it was found that an increase along
the
y
-axis reduced physical stability and an increase along the
x
-axis reduced dissolution
rate. The plot area was then divided into four sections depending on the API properties,
such as propensity for drug to crystallize at high
T
m
/
T
g
or limited API loading due to
dissolution rate at high log
P
. Based on these properties, suggested polymer loadings are
incorporated into the plot for each section. More research is needed to determine whether
this approach will work for other polymers, but it can be used to help guide the polymer
selection process.
Figure 3.2.
T
m
/
T
g
versus log
P
for 139 low-solubility compounds successfully formulated
as amorphous solid dispersions with HPMCAS. (Reproduced with permission from Ref. 6.
Copyright 2008, American Chemical Society.)
