Chemistry Reference
In-Depth Information
dispersions are hydrophilic in nature and contain polar functional groups, and thus can
absorb moisture from the atmosphere. The total water content in an amorphous solid
dispersion can be quantitatively measured using standard approaches such as direct or
oven-assisted Karl Fischer titrations for purposes of quality control testing [46]. In
pharmaceutical development, the measurement of the level of water with a particular
dispersion can be critical because the presence of water can have a plasticizing effect that
can lower
T
g
and increase mobility in the dispersion at a given temperature [47,48]. The
increase in mobility can potentially be detrimental to chemical or physical stability.
More fundamental information about the interaction between moisture and a solid
can be obtained by measuring water sorption and desorption isotherms. The technique
known as gravimetric vapor sorption (GVS) or dynamic vapor sorption (DVS) is the
most common approach used for measurement of sorption isotherms [48]. The GVS
instrument integrates a relative humidity (RH)- and temperature-controlled environment
with a sensitive balance to measure sample mass as a function of RH in a convenient
manner. An older, less convenient approach to the same measurement that is still
employed, particularly when long RH equilibration periods are needed, involves placing
preweighed samples into sealed chambers containing saturated salt solutions with known
RH values [49]. This method can be used to obtain the equilibriummoisture uptake for an
amorphous solid dispersion at a given humidity (e.g., 60% RH) and temperature, either
gravimetrically or by performing a water content measurement such as a Karl Fischer
titration after storage of the dispersion for an extended period. Unlike salt chambers,
GVS instruments can also perform unique humidity ramping experiments to study
processes such as recrystallization from amorphous solid dispersions. The use of GVS is
facilitated for amorphous solid dispersion studies because instruments are widely
available in many analytical laboratories due to their range of applications; for example,
methods based on GVS are often used to quantify amorphous forms at low levels in
crystalline drug substances [50].
The adsorption of water vapor in an amorphous solid dispersion can be modeled up
to an RH of about 40% using the well-known Brunauer
Teller (BET) equation
that is also used for modeling of crystalline solids [48]. The full RH range can be modeled
for many amorphous substances using an extended form of the BET equation known as
the Guggenheim
-
Emmett
-
de Boer (GAB) equation (or simply the Anderson equa-
tion) [48,51]. Over a range of relative pressures (
P
/
P
0
), the GAB equation accounts for
adsorption of water through the processes of initial site adsorption, intermediate bound
water states, and condensation at higher RH:
-
Anderson
-
P
0
W
m
C
G
K
P
=
W
;
(4.5)
P
0
P
0
P
0
1
K
P
=
1
K
P
=
C
G
K
P
=
where
W
is the mass of water absorbed per gram of solid at a relative pressure (
P
/
P
0
),
W
m
is the capacity of an adsorption monolayer,
K
is a constant given by
K
B
exp
H
L
H
m
RT
;
(4.6)
