Bioerodible devices

FIGURE 6 Schematic representation of water intrusion and erosion for one side of a bioerodible device. (From Ref. 18.)... 

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... 

Some implantation devices have extended well beyond the classic diffusional systems and have included not only bioerodible devices, but also implantable therapeutic systems that can be activated. There are devices activated by change in osmotic pressure to deliver insulin [225], morphine release trigger by vapor pressure [226], and pellets activated by magnetism... 

Zygourakis, K., Markenscoff, P.A., 1996. Computer-aided design of bioerodible devices with optimal release characteristics a cellular automata approach. Biomaterials 17, 125—135. 

In bioerodible drug delivery systems various physicochemical processes take place upon contact of the device with the release medium. Apart from the classical physical mass transport phenomena (water imbibition into the system, drug dissolution, diffusion of the drug, creation of water-filled pores) chemical reactions (polymer degradation, breakdown of the polymeric structure once the system becomes unstable upon erosion) occur during drug release. 

Monolithic Devices—In these systems the drug is homogeneously dispersed within a bioerodible polymer matrix, and release of the drug can be controlled either by diffusion or by polymer erosion. If erosion of the matrix is very much slower than drug diffusion, then release kinetics follow the Higuchi model (37) and drug release rate decreases exponentially with time, following t dependence over a major portion of the release rate. 

Release of naltrexone. The ClOlct polymer has been investigated as a bioerod-ible naltrexone delivery system [17]. In this study 20 wt% naltrexone was dispersed into the polymer, pressed into films and 1 x 1 x 14 mm devices punched from the films using a heated punch. Although not stated, the devices very likely also contained 10 wt% Na2C03. Sterilization was achieved by 60Co 2.5 mrad irradiation. 

However, these in vitro studies were carried out in a citrate buffer. When the studies were repeated in a physiologic buffer, response of the device was only minimal, even at very low pH pulses. A more detailed study using two different buffers at various concentrations and at constant pH is shown in Fig. 22 [39]. These data clearly show general acid catalysis and also show that the desired behavior can only be achieved in a citrate buffer. Thus, further work with this polymer was discontinued and a search for another bioerodible polymer that will undergo specific hydronium ion catalysis is currently underway. 

The availability of polymers having different delay times makes possible the construction of devices that can release proteins in well defined and well spaced pulses. To do so, it is only necessary to use a device that contains two or more different polymer formulations in separate domains. This can be achieved by placing these formulations in a thin, bioerodible, macroporous cylinder for subsequent implantation, or better, t.o encapsulate each formulation in a bioerodible, macroporous membrane. In this latter approach, desired release profiles can be achieved by using appropriate mixtures of different capsules. 

A second class of biodegradable polymers of interest are those used in the human (or animal) body. These polymers include those used in artificial organs, other implants, and controlled release devices for delivery of pharmaceuticals. Being placed in contact with the tissue environment, they can potentially biodegrade. In products such as biodegradable sutures and bioerodible drug-delivery matrices, such breakdown in the body may be undesirable. 

Zygourakis, K., 1990. Development and temporal evolution of erosion fionts in bioerodible controlled release devices. Chemical Engineering Science 45, 2359—2366. 

Because of possible adverse effects or a desire to terminate therapy, implanted bioerodible drug delivery systems should be easily removable at any time. For this reason, solid devices that maintain their mechanical integrity throughout the major portion of their delivery regime are particularly attractive. A further desirable feature is drug release that is close to zero order. 

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. ... 

The principal focus of our work is the development of a sub-dermally implantable, bioerodible monolithic device that would release contraceptive steroids by close to zero order kinetics for at least six months. Also, polymer erosion and drug release should be coupled so that no pol3iTner remains in the tissue after all the drug has been released. 

For the analysis of bioerodible polymers, the atomic force microscope (AFM) is more suited than the STM because its imaging mechanism is independent of electron conduction and hence insulating organic materials can be directly visualized (Burnham and Colton, 1993). The basic components of an AFM are shown in Figure 7. The sample is mounted onto a piezoceramic scanner device capable of moving the sample in all three-dimensions. Above the sample surface is the AFM probe unit, which is composed of a sharp probe positioned on the end of a flexible cantilever. The cantilever is microfabricated in a V-shape with the two arms of the V attached to a stationary support. 

---