Biomedical Engineering Reference
In-Depth Information
Therefore to predict the release behavior of drug molecules, the variable diffusivity
needs to be studied with respect to the degree of degradation. The time dependent dif-
fusivity in a degrading region is studied by Porter [116]:
D
(
t
) =
D
(
t
= 0) + {[
D
water
-
D
(
t
= 0)] ×
W
(
t
) × [100% - CRSTL(
t
)]}
(5.148)
where
W
(
t
) is the film's weight loss at time
t
, and CRSTL(
t
) is the coating's degree of
crystallinity.
Prabhu and Hossainy [75] used numerical simulation to study the degradation and
drug release behavior simultaneously. The time-dependent diffusivity was given as an
exponential function with respect to the concentration of the degrading polymer in the
system.
Another type of degradation kinetics is ion exchange. Ion-exchange microspheres are
polymeric microspheres formed by electrostatic attraction between oppositely charged
polymers. The microsphere can be degraded in electrolyte solutions when electrolytes
from a solution replace the polymer in the microsphere (hence the name ion exchange).
Ionic drugs can be easily loaded, and its release is controlled by two factors: diffusion of
the drug and degradation of the microsphere. Besides diffusion barrier, coating can be
used to block electrolytes from entering the microspheres to slow down the degradation
process [76]. Coated ion-exchange formulation offers a better release rate controllabil-
ity. In such a configuration, the release rate is controlled by (1) drug diffusivity in the
matrix and (2) drug diffusivity in the coating. The overall release profile depends on the
limiting step only. If (1) is the rate-limiting step, the core/matrix swells upon contacting
with water; hence the drug diffusivity in the matrix gradually increases. Moreover, the
net flux is governed by both Brownian motion and electric coupling of ionic flux. It was
shown that swelling of the matrix did not have significant effect on the release profile,
but the ionic flux affects the release rate more significantly [77].
Osmotic Pressure Controlled
When a semipermeable coating is applied to a drug containing core, only water molecules
are allowed to diffuse into the core, but the core materials and the drug are retained inside;
therefore, the pressure inside the core will increase. If orifices are drilled in the coating,
the content in the core will be pushed out due to the hydrodynamic pressure built up by
water uptake.
The release kinetics of osmotic pressure controlled system can be described by the fol-
lowing equation [78]:
d
d
M
t
AP
∆
π
C
t
=
W
d
(5.149)
l
where the left-hand side of the equation is the release rate of the drug.
A
is the surface area of
the device,
P
W
is the water permeability of the coating,
Δπ
is the osmotic pressure gradient
across the membrane,
l
is the thickness of the coating, and
C
d
is the drug concentration in
the core.
As can be seen from the equation, surface area and thickness of the coating are device
parameters that can be easily applied. However, water permeability and osmotic pressure
