Bulk erosion, drug release rate

Although it was possible to achieve constant in vitro release of levonorgestrel for up to 410 days at which point the experiment was discontinued, release of the drug was not controlled by surface erosion of the polymer but instead the device underwent bulk erosion and release of levonorgestrel was completely controlled by its rate of dissolution. Bulk erosion of the rod-shaped device was evident by scanning electron microscopy as shown in Fig. 17. 

Drug release rate for matrices undergoing bulk erosion is nonlinear and difficult to predict because it is determined by a combination of diffusion and erosion. However, drug release from devices undergoing surface erosion is predictable and can lead to zero order-kinetics provided diffusional release of the drug is minimal and the overall surface area of the device remains essentially constant. 

A much more desirable erosion mechanism is surface erosion, where hydrolysis is confined to a narrow zone at the periphery of the device. Then, if the drug is weU-immobihzed in the matrix so that drug release due to diffusion is minimal, the release rate is completely controlled by polymer erosion, and an ability to control erosion rate would translate into an ability to control dmg delivery rate. For a polymer matrix that is very hydrophobic so that water penetration is limited to the surface (thus Hmiting bulk erosion), and at the same time, allowing polymer hydrolysis to proceed rapidly, it should be possible to achieve a drug release rate that is controlled by the rate of surface erosion. Two classes of biodegradable polymers successfully developed based on this rationale are the polyanhydrides [31] and poly (ortho esters) [32], the latter of which is the subject of this chapter. 

Because surface erosion results in constant and predictable rate of drug release, this type of erosion is clearly preferrable to bulk erosion. However, to achieve surface erodibility, a system must be devised in which the rate of polymer degradation at the surface of a device is very much faster than the rate of degradation in the interior. 

Figure 2 (a) Bulk erosion of biodegradable controlled-release polymer implants leads to unpredictable release profiles, (b) Polymers exhibiting surface erosion release drug at nearly constant rate (zero-order kinetics) as they dissolve in water. (From Ref. 61.)... 

Based on the chemical structure of the polymer backbone, erosion can take place by either surface or bulk erosion. Surface erosion take place when the tempo of erosion surpasses the tempo of water permeation into the bulk of the polymer and is desirable since the kinetics of erosion and rate of drug release are extremely reproducible. 

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