Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 285

hydrogel was released slowly and equilibrium was reached after 15 h, while chitosan
hydrogel, as a control, released almost all of the p -nitrophenol within several hours [116]. It
was suggested that a chitosan-g-cyclodextrin may serve as a promising carrier for con-
trolled release of hydrophobic drugs.
6.6 Drug Release
6.6.1 Drug release Mechanisms
Understanding the mechanisms and identifying the key parameters that govern drug
release from hydrogels are the most important in order to accurately predict the entire
release profile. Drug release behaviors from hydrogels are very different from nonhydro-
philic polymers due to their hydrophilicity and high water absorbability. From various
modelistic studies on the possible release mechanisms of an active agent from a hydrogel,
as a function of time, focused on the rate-limiting step of the release phenomena, drug
release mechanisms from hydrogels can be classified into the following: diffusion-
controlled, swelling-controlled, and chemically controlled mechanisms [117].
6.6.1.1 Diffusion-Controlled Mechanism
The diffusion-controlled mechanism is the most widely applicable mechanism to describe
drug release from hydrogels. Fick's law of diffusion with either constant or variable diffu-
sion coefficients is commonly used in modeling diffusion-controlled release [118].
Diffusion-controlled hydrogel delivery systems can be either reservoirs or matrixes. Fick's
first law of diffusion is usually used to describe a reservoir release system, whereas Fick's
second law of diffusion is used to describe a matrix system [117]. Diffusion coefficient is an
empirical parameter, usually assumed to be constant to simplify the modeling. Once the
diffusion coefficient is determined, drug concentration profiles can be obtained to dictate
the drug release kinetics. However, Fick's law is not available when more complex geom-
etries or nonconstant drug diffusivities are incorporated into the model [117].
Drug diffusion out of a hydrogel matrix is primarily dependent on mesh sizes within
the matrix of the gel [118]. Actually, molecule diffusion coefficient is related to hydrogel
characteristics. That is, hydrogel characteristics, such as structure of the gel, polymer
composition, water content, and size of the drugs, are taken into account as factors influ-
encing the drug release profile. It was reported that typical mesh sizes for biomedical
hydrogels range from 5 to 100 nm in their swollen state [4], which is much larger than the
size of most small-molecule drugs. Therefore, the diffusion of small-molecule drugs is not
significantly hindered in the swollen state, whereas macromolecules such as protein and
peptides, due to their hydrodynamic radii, will not have a sustained release unless the
structure and mesh size of the swollen hydrogels are designed appropriately to obtain the
desired rates of macromolecular diffusion [118].
6.6.1.2 Swelling-Controlled Mechanisms
Another mechanism for drug delivery is swelling-controlled delivery. Hydrogels may
undergo a swelling-driven phase transition from a glassy state where entrapped molecules
remain immobile to a rubbery state where molecules rapidly diffuse. When diffusion of