Drugs, surface-erosion mechanism

Convincing evidence for a surface erosion process is shown in Fig. 8, which shows the concomitant release of the incorporated marker, methylene blue, release of the anhydride excipient hydrolysis product, succinic acid, and total weight loss of the device. According to these data, the release of an incorporated drug from an anhydride-catalyzed erosion of poly (ortho esters) can be unambiguously described by a polymer surface erosion mechanism. 

Poly(ortho esters) were first developed by the ALZA corporation (Alzamer) in 1970 in order to seek new synthetic polymer for drug delivery applications. These polymers degrade by surface erosion and degradation rates may be controlled by incorporation of acidic or basic excipients. The polymer is hydrophobic enough such that its erosion in aqueous environments is very slow. The unique features of poly(ortho esters), in addition to their surface erosion mechanism, is the rate of degradation for these polymers, pH sensitivity, and glass transition temperatures, which... 

Figure 5.1 A systematic representation of polyanhydride drug carriers and their applications, (a) The types of the polyanhydrides — conventional and advanced, (b) various carrier systems fabricated using different polyanhydrides, (c) various classes of biologicals and non-biologicals utilising polyanbydrides for their delivery, (d) products related to polyanhydrides which have reached from bench to clinic, (e) surface erosion mechanism of polyanhydrides and the typical zero-order release profile.

Another mechanism for modulated drug release is local pH-induced surface erosion of interpolymer complex gels with entrapped solutes, as shown in... 

In their study of branched PSA, Maniar et al. (1990) found that the molecular architecture of branched polymers affects the release kinetics in a variety of ways. They found that the branched polymers degraded faster than linear PSA of comparable molecular weight (Maniar et al., 1990). They also noted that drug (morphine) release profiles were more characteristic of bulk erosion than surface erosion An initial lag time during which very little drug was released was associated with the time required for water to swell the polymer. This was followed by a period of relatively fast release, which tapered off as the device disintegrated. The polymer matrix lost its mechanical integrity before the release experiment was complete (Maniar et al., 1990). Despite the increase... 

P. I. Lee, Initial Concentration Distribution as a Mechanism for Regulating Drug Release from Diffusion Controlled and Surface Erosion Controlled Matrix Systems,... 

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. 

The potendal of the AFM to enhance the characterization of bioerodible polymers, and biomaterials in general, stems from ability of the instrument to obtain veity high resolution images from uncoated polymer. samples within aqueous environments. Therefore, it has become possible to image dynamic processes like surface erosion and protein adsorption which are fundamental to the mechanisms of drug delivery and biocompatibility. 

In the erosion mechanism, the SDD particle does not disintegrate, but rather erodes from the surface to generate supersaturated free drug species and dissolved polymer chains. Typically, no nanoparticles are formed when this mechanism occurs, and performance usually is tied to the size and surface area of the particles, since the mechanism is a surface phenomenon. 

---