Chemistry Reference
In-Depth Information
were mixed in an agar controlled-release matrix. From understanding the interaction
parameters between surfactants and polymers, ASDs for both immediate- and controlled-
release pro
les may be tailored, while maintaining supersaturation of the drug.
In addition to understanding the thermodynamic interactions between the API
solute and excipient systems, which affect both physical stability in the ASD and API
solubility, determining the kinetics of API dissolution is also important, which
ultimately in
uences the bioavailability of the drug in the GI tract. The dissolution
rate of a drug (d
M
/d
t
) from a solid matrix as a function of time can be described by the
Noyes
-
Whitney equation [48]:
d
M
d
t
DA
h
C
0
C
t
:
(2.7)
The dissolution rate is in
uenced by various factors such as its diffusivity from a solid
matrix into the solution phase (
D
), surface area (
A
), boundary layer thickness (
h
),
equilibrium solubility (
C
0
), and concentration in solution at time
t
(
C
t
). As a drug is
finely dispersed within the excipients down to its molecular size, the resistance for
dissolution and diffusion is reduced and its surface area to volume ratio increases.
The expression to determine the rate of the
phases during
dissolution can be generally derived by comparing the dissolution pro
“
spring
”
and
“
parachute
”
les of the
theoretical amorphous and crystalline phases with the
amorphous solid system
in the presence of crystallizing drug. Figure 2.14 shows the typical shape of dissolution
pro
“
real
”
les of the various drug forms.
The initial rise in drug concentration
x
can be related to time
t
by the
“
spring
”
rate
constant
K
s
(where
x
K
s
t
). Assuming that
X
a
(pure amorphous drug in solution) is
X
c
(pure crystalline drug in solution), the rate constant
K
s
can be de
=
ned as [46b]
Figure 2.14.
Dissolution pro
les of
three types of drug species: ideal
amorphous (
X
a
), “real” amorphous/
supersaturated (
X
a,ideal
), and ideal
crystalline (
X
c
). (Adapted from
Ref. 46b.)
