Bulk erosion

Biodegradation of the aliphatic polyesters occurs by bulk erosion. 

When a hydrophobic polymer with a physically dispersed acidic excipient is placed into an aqueous environment, water will diffuse into the polymer, dissolving the acidic excipient, and consequently the lowered pH will accelerate hydrolysis of the ortho ester bonds. The process is shown schematically in Fig. 6 (18). It is clear that the erosional behavior of the device will be determined by the relative movements of the hydration front Vj and that of the erosion front V2- If Vj > V2, the thickness of the reaction zone will gradually increase and at some point the matrix will be completely permeated with water, thus leading to an eventual bulk erosion process. On the other hand, if V2 = Vj, a surface erosion process wiU take place, and the rate of polymer erosion will be completely determined by the rate at which water intrudes into the matrix. 

Because swelling and consequent bulk erosion induced by the water-soluble salt is not desirable, use of the low-water-solubility, sUghtly acidic salt calcium lactate was investigated (30). By using this excipient it was hoped that a lowering of the pH within the surface layers of the device would take place and release of the drug would be controlled by polymer erosion confined to the surface layers of the device. In these experiments norethindrone was replaced by the currently favored steroid levonorgestrel. 

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. 

At the time these studies were conducted, the role of acidic excipients was not clearly understood, but the observed bulk erosion is of course consistent with the mechanism shown in Fig. 6. Consequently, if gross bulk erosion is to be avoided and long-term erosion control of levonorgestrel achieved, it is necessary to stabilize the device interior. To do so, devices with incorporated Mg(OH)2... 

Erosion is typically characterized by either occurring on the surface or in the bulk. Surface erosion is controlled by the chemical reaction and/or dissolution kinetics, while bulk erosion is controlled by diffusion and transport processes such as polymer swelling, diffusion of water through the polymer matrix, and the diffusion of degradation products from the swollen polymer matrix. The processes of surface and bulk erosion are compared schematically in Fig. 1. These two processes are idealized descriptions. In real systems, the tendency towards surface versus bulk erosion behavior is a function of the particular chemistry and device geometry (Tamada and Langer, 1993). Surface erosion may permit the... 

Fig. 1. Schematic comparing surface and bulk erosion. In surface erosion (top), water does not penetrate far into the bulk, but hydrolyzes functional groups on the surface. The resulting monomers dissolve and diffuse away from the device. In bulk erosion (bottom), water penetrates into the bulk, polymer may dissolve, and is ultimately hydrolyzed into monomer.

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... 

Biodegradation of the aliphatic polyesters occurs by bulk erosion. The lactide/gly-colide polymer chains are cleaved by random nonenzymatic hydrolysis to the monomeric lactic and glycolic acids and are eliminated from the body through the Krebs cycle, primarily as carbon dioxide and in urine. 

Bulk elastic modulus, of binary compound semiconductors, 22 145, 146-147t Bulk enzymes, from genetically engineered microbes, 22 480 Bulk erosion, 9 78 Bulk fluid velocity method, 16 688 Bulk gallium nitride, supercritical ammonia solution growth of, 14 96-97 Bulk gases... 

Hydrolysis of the polymers can be affected by spontaneous degradation of the material from the surface or the bulk or by enzymatic hydrolysis. Copolymers of lactic acid and glycolic acid (PLGA) are by far the most common biocompatible polymers that undergo bulk erosion by... 

Diffusion control Reservoir system Monolithic matrix Matrix degradation Surface erosion Bulk erosion Osmosis Ion exchange Enzymatic cleavage Hydrolytic degradation... 

Matrix degradation for controlled drug release (A) bulk erosion of a matrix, (B) surface erosion of a matrix. Source. From Ref. 34. 

In bulk erosion, the entire area of polymer matrix is subject to chemical or enzymatic reactions, thus erosion occurs homogeneously throughout the entire matrix Accordingly, the degradation pattern is sometimes termed homogeneous erosion. 

Polyesters, such as poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA), are examples of biomaterials that are degraded by homogeneous bulk erosion. 

Which one of the following polymers undergoes homogeneous bulk erosion (a) Poly(lactide-co-glycolide) (b) Poly[bis(p-carboxyphenoxy)propane sebacic acid) (c) Poly(ortho esters) and/or (d) Poly(ethylene-vinyl acetate). 

Hydrolytic erosion Phase I surface erosion Phase II bulk erosion... 

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. 

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. 

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