Diffusion-controlled release

In this case, the drug must diffuse through either a polymeric membrane or polymeric or lipid matrix, in order to be released. Diffusion-controlled devices can be divided into (Figure 3.1) ... 

Release Diffusion controlled Diffusion and Diffusion to erosion... 

The vapor cloud of evaporated droplets bums like a diffusion flame in the turbulent state rather than as individual droplets. In the core of the spray, where droplets are evaporating, a rich mixture exists and soot formation occurs. Surrounding this core is a rich mixture zone where CO production is high and a flame front exists. Air entrainment completes the combustion, oxidizing CO to CO2 and burning the soot. Soot bumup releases radiant energy and controls flame emissivity. The relatively slow rate of soot burning compared with the rate of oxidation of CO and unbumed hydrocarbons leads to smoke formation. This model of a diffusion-controlled primary flame zone makes it possible to relate fuel chemistry to the behavior of fuels in combustors (7). 

Kodama and Brydon [631] identify the dehydroxylation of microcrystalline mica as a diffusion-controlled reaction. It is suggested that the large difference between the value of E (222 kJ mole-1) and the enthalpy of reaction (43 kJ mole-1) could arise from the production of an amorphous transition layer during reaction (though none was detected) or an energy barrier to the interaction of hydroxyl groups. Water vapour reduced the rate of water release from montmorillonite and from illite and... 

In vitro release of methotrexate from the LDI based films is shown in Figure 7. The release was fast since the drug was imbedded in a thin film, in the order of 50 to 100 microns. The release profile was typical of one seen in diffusion controlled systems. The scattering of the release data was again reminiscent of the mass loss results, and the cause of that is not certain at this point... 

The rate and type of release can be analyzed by the expression Mt/Moo=ktn (76). In the case of pure Fickian diffusion n = 0.5, whereas n > 0.5 indicates anomalous transport, i.e., in addition to diffusion another process (or processes) also occurs. If n = 1 (zero order release), transport is controlled by polymer relaxation ("Case II transport") (76). The ln(Mt/Mco) versus In t plots, shown in Figure 4, give n = 0.47 and 0.67 for samples A-9.5-49 and A-4-56, respectively. Evidently theophylline release is controlled by Fickian diffusion in the former network whereas the release is... 

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... 

Matrix diffusion-controlled system in which the drug is homogeneously dispersed in a hydrophilic polymer diffusion from the matrix controls release rate Nitrodur (nitroglycerin key). 

GWR Davidson IH, NA Peppas. Solute and penetrant diffusion in swellable polymers. VI. The Deborah and swelling interface numbers as indicators of the order of biomolecule release. J Controlled Release 3 259-271, 1986. 

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 ... 

As was mentioned in the introduction to this chapter "diffusion-controlled dissolution" may occur because a thin layer either in the liquid film surrounding the mineral or on the surface of the solid phase (that is depleted in certain cations) limits transport as a consequence of this, the dissolution reaction becomes incongruent (i.e., the constituents released are characterized by stoichiometric relations different from those of the mineral. The objective of this section is to illustrate briefly, that even if the dissolution reaction of a mineral is initially incongruent, it is often a surface reaction which will eventually control the overall dissolution rate of this mineral. This has been shown by Chou and Wollast (1984). On the basis of these arguments we may conclude that in natural environments, the steady-state surface-controlled dissolution step is the main process controlling the weathering of most oxides and silicates. 

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