Biomedical Engineering Reference
In-Depth Information
6
Experimental results
Fitting curve
5
4
R
2
= 0.96
3
2
1
0
10
20
30
40
50
60
70
C
M, immob
(mg/ml)
FIGURE 5.9
Partition-coefficient curve.
The partition coefficient equation was successfully fitted to experimental data as shown
in Figure 5.9 [70].
Another approach to control release rate by partition/solubility control is to alter pH
values of the microenvironment of the coating so as to tailor the protein solubility in it.
It is widely known that basic drugs have higher solubility in acidic environment and
vice versa, and only dissolved drug can be released. Hence pH modifiers (fumaric, tar-
taric, adipic, glutaric, and sorbic acid) have been added into the coating for release rate
control [71].
Erosion Controlled
In a biodegradable coating configuration, there are a couple of mechanisms that the release
rate can be tailored: (1) dense coating so that drug can only be released upon degradation of
the coating; (2) coarse coating, in which the drug has a smaller but noticeable diffusivity; and
(3) drug containing coating that drug can be released from the coating when degradation
occurs. In situation (1), the coating serves as a complete diffusion barrier so that solution-
diffusion model discussed in the previous section is no longer valid. The control over
release rate is pulsatile: as long as the coating completely covers the drug carrier, there
is no drug being released. Once the carrier is exposed to the external environment, the
release rate will not be significantly affected by the residual coating left on the surface. In
situation (2), the release behavior is more complicated. The coating serves as a solution-
diffusion coating with two exceptions: thickness and pore size change with time. As more
coating is degraded, thickness of the coating might change, and when the cross-links are
hydrolyzed, the pore size is increased, so that drug diffusivity and partition coefficient are
both affected. In situation (3), release rate is solely determined by the degradation rate and
the drug loading level.
Diffusion is again an important factor to affect the rate of degradation: reagents need to
enter the matrix to hydrolyze the cross-links; on the other hand, products of the hydrolysis
reaction need to diffuse out to facilitate the reaction toward degradation. Besides diffu-
sion, degradation kinetics affects the overall degradation rate as well.
