Diffusion-controlled release mechanisms

The slope is indicative of the type of release mechanism. A slope of 0.5 indicates a diffusion-controlled release a slope of 1.0 indicates that a corrosion-related mechanism is operable.The diffusion release mechanism is characterized by surface adsorption, ion exchange, and migration. Chemical corrosion, or alteration of the silicate lattice, is characterized by hydroxyl attack on silicon or by hydrogen attack on bridging oxygens. 

Equation (6.94) illustrates that zero-order release kinetics are obtained if drug dissolution controls the release kinetics. However, as soon as the last particle in the matrix dissolves, the controlling mechanism of drug release shifts to Fickian diffusion. Figure 6.19 shows the dissolution-controlled release of KC1 at the early stage of release and the diffusion-controlled release at the later stage of release from an ethyl cellulose tablet. 

The area of applied bioactive polymeric systems includes such diverse entities as controlled release systems (erodable systems, diffusion controlled systems, mechanical systems and microcapsules), and biologically active polymers, such as natural polymers, synthetic polypeptides, pseudo-enzymes, pseudo-nucleic acids and polymeric drugs. The area can also include immobilized bioactive materials, such as immobilized enzymes, antibodies and other bioactive agents and the area of artificial cells. This Chapter reviews the general field of biologically active synthetic and modified natural macromolecules with an emphasis on their common characteristics, problems and applications. The areas reviewed include both medical and non-medical applications for both controlled release systems and polymers that exhibit direct biological activity. 

Root exudation of extraordinary high amounts of specific carboxy lutes (e.g ci-u-ate, malate. oxalate, pbytosiderophores) in response to nutritional deficiency stress or Al toxicity in some plant species cannot simply be attributed to diffusion processes. The controlled release of these compounds, involved in mobilization of mineral nutrients and in detoxification of Al. may be mediated by more specific mechanisms. Inhibitory effects by exogenous application of various anion chan-... 

However, in the foregoing systems, the predominant mechanism allows easy mathematical description. In practice, the dominant mechanism for release will overshadow other processes enough to allow classification as either dissolution rate-limited or diffusion-controlled. Bioerodible devices, however, constitute a group of systems for which mathematical descriptions of release characteristics can be quite complex. Characteristics of this type of system are listed in Table 7. A typical system is shown in Fig. 8. The mechanism of release from simple erodible slabs, cylinders, and spheres has been described [36], A simple expression describing release from all three of these erodible devices is... 

Mechanisms of dissolution kinetics of crystals have been intensively studied in the pharmaceutical domain, because the rate of dissolution affects the bioavailability of drug crystals. Many efforts have been made to describe the crystal dissolution behavior. A variety of empirical or semi-empirical models have been used to describe drug dissolution or release from formulations [1-6]. Noyes and Whitney published the first quantitative study of the dissolution process in 1897 [7]. They found that the dissolution process is diffusion controlled and involves no chemical reaction. The Noyes-Whitney equation simply states that the dissolution rate is directly proportional to the difference between the solubility and the solution concentration ... 

The effect of variability in fluoride release between hand-mixed and cap-sulated systems was studied by Verbeeck et al. [266] who found that the mean value and variance of fluoride release were greater for the capsulated system than for the hand-mixed system. A two-process mechanism, consisting of a short-term elution (with a half life of nine hours) followed by diffusion controlled long-term release, for the release of F was suggested based on an empirical correlation of the data. The differences in the amounts of F released are attributed to the different mixing processes. 

Another important consequence of the constant rate of release diffusion model is that it mimics many of the features that have commonly been attributed to surface reaction (matrix dissolution) control. If one were to account for changes in surface area over time, the predicted long-term dissolution rate due to surface reaction control would also yield constant element release. In surface reaction controlled models, the invariant release rate with respect to time is considered to be the natural consequence of the system achieving steady-state conditions. Other features of experiments commonly cited as evidence for surface reaction control, such as relatively high experimental activation energies (60-70 kJ/ mol), could be explained as easily by the diffusion-control model. These findings show how similar the observations are between proponents of the two models it is only the interpretation of the mechanism that differs. 

Goodness-of-fit analysis applied to release data showed that the release mechanism was described by the Higuchi diffusion-controlled model. Confirmation of the diffusion process is provided by the logarithmic form of an empirical equation (Mt/ M=ktn) given by Peppas. Positive deviations from the Higuchi equation might be due to air entrapped in the matrix and for hydrophilic matrices due to the erosion of the gel layer. Analysis of in vitro release indicated that the most suitable matrices were methylcellulose and glycerol palmitostearate. 

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