Erosion, release

FIGURE 5 Erosion release profile for radioactive progesterone from a a mixed-substituent imidazolyl/p-methylphenoxyphosphazene polymer. 31.)... 

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.)... 

Some tablets that provide a sustained period (up to 8—12 h) of therapy may be coated during processing. A portion is released first to bring the dmg to the desired blood concentration (onset of activity), whereas a sustained-release portion maintains an effective level for a prolonged period of time (duration of activity), eg, by coating erosion or diffusion of dmg through it. 

An example is poly(bis(p-carboxyphenoxy)propane) (PCPP) which has been prepared as a copolymer with various levels of sebacic anhydride (SA). Injection molded samples of poly (anhydride) / dmg mixtures display 2ero-order kinetics in both polymer erosion and dmg release. Degradation of these polymers simply releases the dicarboxyhc acid monomers (54). Preliminary toxicological evaluations showed that the polymers and degradation products had acceptable biocompatibiUty and did not exhibit cytotoxicity or mutagenicity (55). 

The theoretical maximum suction lift at sea level for water (14.7 psi) (2.31 fi/psi) = 34 ft. However, due to flow resistance, this value is never attainable. For safety, 15 feet is considered the practical limit, although some pumps will lift somewhat higher columns of water. WTen sealing a vacuum condition above a pump, or the pump pumps from a vessel, a seal allowance to atmosphere is almost always taken as 34 feet of water. High suction lift causes a reduction in pump capacity, noisy operation due to release of air and vapor bubbles, vibration and erosion, or pitting (cavitation) of the impeller and some parts of the casing. (The extent of the damage depends on the materials of construction.)... 

Carbon is released from the lithosphere by erosion and resides in the oceans ca. 10 years before being deposited again in some form of oceanic sediment. It remains in the lithosphere on the average 10 years before again being released by erosion (Broecker, 1973). The amount of carbon in the ocean-atmosphere-biosphere system is maintained in a steady state by geologic processes the role of biological processes is, however, of profound importance... 

The influence of polymer composition and molecular weight on the estrus-suppressing activity of the microspheres in female rats was determined. A triphasic release pattern was observed. An initial rapid release over the first few days was attributed to diffusion from superficial areas of the microspheres. A second phase of lower release levels then occurs and continues until the onset of the third, major phase of release. This phase is facilitated by the onset of erosion of the polymer matrix. 

The rate of polymer erosion in the presence of incorporated anhydride and release of an incorporated drug depends on the pK of the diacid formed by hydrolysis of the anhydride and its concentration in the matrix (20). This dependence is shown in Fig. 7 for 2,3-pyridine dicarboxylic anhydride and for phthaUc anhydride. In this study, methylene blue was used as a marker. The methylene blue release rate depends both on the pK and on the concentration of diacid hydrolysis product in the matrix. However, at anhydride concentrations greater than 2 wt%, the erosion rate reaches a limiting value and further increases in anhydride concentration have no effect on the rate of polymer hydrolysis. Presumably at that point Vj, the rate of water intrusion into the matrix, becomes rate limiting. 

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. 

Surface erosion not only leads to zero-order drug release from devices that maintain a constant surface area, but has other important consequences. Among these are the following (1) the rate of drug release is directly proportional to drug loading, (2) the lifetime... 

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