Biomedical Engineering Reference
In-Depth Information
For charged coatings, the release behavior depends on the polarity and thickness of the
coating. Zhou and coworkers [126] coated PLGA microspheres with electrolytes of different
polarities. Their findings were that the release rate of charged molecules decreased with
increases in coating thickness, but layer thickness had little effect on neutral molecules.
The outer layer polarity had a more prominent effect on the drug release rate because
the charging state of the coating is determined by the outermost layers. Molecules with
opposite charge compared to the outermost layer had slower release rate due to the strong
binding.
Schwartz et al. [108] studied the effect of coating level on the release kinetics. It was sum-
marized that four different mechanisms might exist for different coating levels [127]:
(1) Thin and uneven coatings: transport of the drug through flaws, cracks, and imper-
fections within the matrix or uncoated systems
(2) Thin and even coatings: transport of the drug through a network of capillaries
filled with release media
(3) Thick and hydrogel: transport of the drug through a hydrated swollen film
(4) Thick and more rigid film: transport of the drug through barriers or nonporous
coatings, which are determined by the permeability of drug in the film
As the coating level (measured by the weight of the coating) gradually increased, the drug
release rate was reduced. A faster release at lower coating levels was attributed to the
incomplete/discontinuous coating. When coating level was high, more of the core sur-
face was covered by the coating material until the whole surface was covered. Core-shell
structure has been used in particulate formulations for release rate control. Winey et al.
[128] studied the chitosan-coated PLGA nanoparticles and found that the burst release
was dramatically reduced even with a single layer of coating by physical absorption. Lee
et
al. studied the effect of plasticizers on the release profile. Plasticizers are used in coating
preparation to alter its mechanical and thermal properties (glass transition temperature,
free volume, brittleness). It was found that the hydrophilicity of the plasticizer itself does
not significantly affect the release profile if they were retained inside the coating, but the
hydrophilic plasticizer could easily leash out from the coating [129].
Kaplan et al. [130] used layer-by-layer assembly of silk onto alginate and PLGA micro-
spheres. The assembly was driven by hydrophobic interaction between silk and the micro-
spheres. It has been shown that the release of model drugs is more linear and last for a
longer period after coating with silk (Figure 5.12).
Dual-layer coating is also used to alter the release rate of drugs. Dashevsky et al.
[94]
coated a drug containing core with Kollicoat SR 30 D as a release rate limiting layer. A PVA
layer is applied in between the core and Kollicoat coating to prevent hydrophobic drug
from partitioning into the outer layer during coating and storage. It has been shown that
drug release rate can be easily controlled by the coating levels (measured by the weight
percentage of coating in the formulation).
In coated microspheres, the release rate of drugs is mainly determined by the coating,
whereas the core serves as nothing but a reservoir. If the core can be removed, a microcap-
sule will be formed for loading hydrophilic drugs. Li [131] used CaCO
3
microspheres as
a template and coated it with poly-l-lysine hydrobromide and chondrotin sulfate sodium
salt (CS) through layer-by-layer assembly. The core was then dissolved in disodium ethy-
lenediaminetetraacetic acid. However, this configuration shows a pH-dependent loading
behavior because the assembly is driven by an electrostatic force; hence, the wall of the
