Biomedical Engineering Reference
In-Depth Information
this reason, sulfate was taken for microsphere formulation. Sulfate leads to a poorly soluble
chitosan derivative, whereby microsphere formulation becomes possible.
Chitosan was always employed at a concentration of 0.25% (w/v). Higher concentrations
were not practical, because the viscosity became too high. As a consequence, a homoge-
neous distribution of the added sodium sulfate was not possible, which would have led to
the formation of agglomerates. The addition of polysorbate 80 was necessary to stabilize
the suspensions. Without polysorbate 80 the formation of agglomerates occurred.
SEM studies confirm that the MW of chitosan has no influence on the size and appear-
ance of microspheres. Microspheres are spherical and regular, with a size between 1.5 and
2.5 μm revealed by the scanning electron micrograph. The surface is smooth.
The chitosan microspheres were charged positively, although sulfate ions were used as
the precipitant. This indicates that only a part of the amino groups are neutralized during
microsphere formation. The residual amino groups would be responsible for the positive
zeta potential. Moreover, these groups are freely accessible for interaction with drugs as
well. The zeta potential was higher at low pH than at high pH. The pH dependence was
st rongest bet ween pH 3 and 6, leveli ng off at pH values above 6. Th is correlated with the dis-
sociation constant of chitosan, which is about 6. MW had no effect on zeta potential. This
was expected because the deacetylation grade of chitosan was not dependent on MW.
The adsorption of prednisolone sodium phosphate (PSP) was 10 times greater than that
of prednisolone. PSP is a hydrophilic drug; therefore, ethanol addition during loading was
not necessary. In addition and probably most importantly, PSP has a negatively charged
phosphate group. This phosphate group presumably led to a powerful interaction of the
drug with chitosan and facilitated the formation of an ion pair. Figure 3.13 shows the
adsorption isotherms of PSP onto microspheres with different MWs. During these adsorp-
tion experiments, the pH of the medium was kept at 4.0 ± 0.2. At this pH, PSP is present in
an anionic form and protonation of the amino groups of chitosan is still considerable.
These conditions lead to an optimal interaction between PSP and chitosan. At lower and
35
30
25
20
15
10
5
0
0
1 2 3
Equilibrium concentration (mg mL -1 )
4
5
6
Figure 3.13
Adsorption isotherms of PSP onto chitosan microspheres: ( ) LMWC; ( ) medium-molecular-weight chitosan;
and ( ) HMW chitosan (mean ± SD; n = 3).
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