Drug release diffusion control

Because PCL hydrolyzes slowly compared to PLA and PLGA, it is most suitable for long-term drug delivery. Capronor , a 1-year contraceptive represents such a system [106]. The release of drugs is diffusion controlled rather than erosion controlled [106]. Nitrofurantoin, an antibacterial agent used in the treatment of urinary tract infections, has been incorporated into PCL microspheres [ 105]. The drug release rate was proportional to the square-root of time, i.e., fol-... 

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) ... 

Solid state drug release systems controlled with coating are called membrane diffusion or reservoir systems [36, 37]. The process of drug release is illustrated in Figure 18.6. The driving force of the process is diffusion and the phenomenon of osmosis [22, 37, 38, 40]. 

Figure 1. Mechanisms of controlled release drug delivery. Diffusion-controlled (A), dissolution-controlled (B), osmoticSly controlled (C), ion-exchange controlled (D), and degradation-controlled (polymeric prodnig, E) systems.

In developing such devices, two fundamentally different approaches are possible. In one, mechanism of drug release is by diffusion from a reservoir through a rate-limiting bioerodible pol3nner membrane, and in the other, drug release is controlled by matrix erosion. However, to achieve zero order drug delivery from monolithic erosional devices the erosion process must be confined to the surface of the solid device. ... 

This short chapter suggests how diffusion and phase changes can sometimes interact. For example, when drug release is controlled by slow drug diffusion across a membrane, the rate of release can be constant if the drug concentration on one side of the membrane is kept saturated, refreshed by the solid drug quickly dissolving. When acid diffuses into a porous solid, the acid can dissolve the solid s surface while it effects precipitation of the same solid below the surface. While the examples discussed here are not exhaustive, they illustrate the more basic ideas in the book that find broad application. 

Ethylene vinyl acetate has also found major applications in drug delivery. These copolymers used in drug release normally contain 30-50 wt% of vinyl acetate. They have been commercialized by the Alza Corporation for the delivery of pilocarpine over a one-week period (Ocusert) and the delivery of progesterone for over one year in the form of an intrauterine device (Progestasert). Ethylene vinyl acetate has also been evaluated for the release of macromolecules such as proteins. The release of proteins form these polymers is by a porous diffusion and the pore structure can be used to control the rate of release (3). Similar nonbiodegradable polymers such as the polyurethanes, polyethylenes, polytetrafluoroethylene and poly(methyl methacrylate) have also been used to deliver a variety of different pharmaceutical agents usually as implants or removal devices. 

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 of drug release (E) from the eroding matrix is controlled by (a) the chemical properties of the system - the hydrolytic and the neutralizing process at the boundary of the device, catalytic degradation of the polymer and the intrinsic backbone reactivity, and (b) several concomitant physical processes such as water diffusivity, water solubility, water partitioning, etc. 

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