Degradation profiles

Recently, Brich and coworkers (40) reported the synthesis of lactide/glycolide polymers branched with different polyols. Polyvinyl-alcohol and dextran acetate were used to afford polymers exhibiting degradation profiles significantly different from that of linear poly-lactides. The biphasic release profile often observed with the linear polyesters was smoothened somewhat to a monophasic profile. Further, the overall degradation rate is accelerated. It was speculated that these polymers can potentially afford more uniform drug release kinetics. This potential has not yet been fully demonstrated. 

The in vitro degradation profiles of several TDI poly(phosphoester-ure thanes) are shown in Figure 2. It is not possible from this study to correlate the decomposition kinetics with the chemical structure, except for the fact that biodegradability is demonstrated. The in vitro release of 5-FU from PPU-7 is shown in Figure 3. After an initial burst, a reasonably steady and sustained release followed. The UV spectrum of the released 5-FU was identical to that of pure 5-FU, suggesting the chemical integrity of the drug. 

Some compounds exhibit pH behavior in which a bell-shaped curve is obtained with maximum instability at the peak [107]. The peak corresponds to the intersection of two sigmoidal curves that are mirror images. The two inflection points imply two acid and base dissociations responsible for the reaction. For a dibasic acid (H2A) for which the monobasic species (HA-) is most reactive, the rate will rise with pH as [HA-] increases. The maximum rate occurs at pH = (pA) + pK2)/2 (the mean of the two acid dissociation constants). Where an acid and base react, the two inflections arise from the two different molecules. The hydrolysis of penicillin G catalyzed by 3,6-bis(di-methylaminomethyl)catechol [108], is a typical example. For a systematic interpretation of pH-degradation profiles, see the review papers by van der Houwen et al. [109] and Connors [110]. 

Incorporation of a 2% level of either ZnSn(OH) or ZnSnO into the resin, leads to marked differences in its thermal degradation profile. The initial decomposition comprises two distinct stages, the major step occurring at a lower temperature than that of the untreated polymer, which may be indicative of promotion of bromine volatilisation by the zinc stannates. Furthermore, the amount of residue burnt off in the char oxidation step is greatly increased in the tin-containing samples, and the temperature at which this process occurs is significantly higher than in the base resin. 

The degradation profile can be detected by measuring a property, such as microhardness, as a function of depth after ageing so that the magnitude of any effect from the limitation of oxygen diffusion could be measured for any temperature and material combination. The effect of a degradation profile on a bulk property will depend on the particular... 

In spite of these disadvantages, some of which appear to be already overcome (Anderson et al., 2003), many successful case-stories of the use of foul-release coatings are available on fast-moving vessels and propellers (Anderson et al., 2003). However, the existence of powerful broad-spectrum synthetic biocides with satisfactory degradation profiles in sea water (e.g. Sea-Nine 211, Zn- and Cu- pyrithiones Yebra et al., 2004) means that chemically-active antifouling coatings will probably dominate the bulk market of AF paints for seagoing vessels for many years to come (Yebra et al., 2004). 

The number of cells present depends on the level of cell growth and cell death. Therefore, detection of cell death is a commonly used approach to average cell growth. Apoptosis induction can be studied most easily by detection of subdiploid cells or analysis of DNA degradation profiles on the flow cytometer after DNA extraction and propidium iodide staining. 

Recently, the reaction between the sulfate radical anion and cyanuric acid, a nondegrad-able end product of the oxidative degradation of the triazine-based herbicide-atrazine, was reported. The degradation profile indicates that about 76% of the cyanuric acid has been decomposed after an absorbed y-radiation dose. It is therefore proposed that the reaction of peroxydisulfate could be utilized for the degradation of cyanuric acid in aqueous medium, which is important, since the latter is normally stable to further organic processes. 

Even when impurities and degradation profiles of a drug substance have been established and containers comply with guidelines, some unexpected drug-container interactions can occur during the sterilization procedure or shelf life. 

Changes in equipment or suppliers of critical supplies of the API or final drug product will have the potential to change their degradation profile and may require the method to be redeveloped and revalidated. 

It is common practice to utilize forced degradation studies to accelerate degradation of the drug substance or drug product to get an understanding of its degradation profile. Potential environmental conditions that can be used include 40°C and 75% relative humidity (RH), 50°C and 75% RH, 70°C and 75% RH, or 80°C and 75% RH. Oxidation, reduction, and pH-related degradations are... 

The method was found to be deficient in some areas, such as precision and system suitability. This is especially important as the analytical laboratory gets more experience and more information as to the degradation profile of the sample as it progresses toward submission. If a new impurity is found that makes the method deficient, this method will need to be revalidated. 

Changes in equipment or in suppliers of critical supplies at the time of manufacturing. This is important, as critical components of the manufacturing process have the potential to change the degradation profile of the product. 

Different isomers may have different rates of degradation in the environment which would change the overall risk. For example, in the case of cypermethrin, the trans-isomers were preferentially degraded over the cis-isomers. Of the two active isomers of this insecticide, the (lR)-ds-(aS)-isomer was degraded more slowly than (1 R)-tmns-(u. S)-i sorn er by bacteria and in whole sediments [150]. By selecting for the isomer (or process that produces a majority of that isomer) with the more rapid degradation profile, the ecological risk should be reduced. 

Figure-6-4 Typical degradation profile (c(DOC)tlc(DOC)lf of a multi-sequential chemical/biologi-cal batch treatment process (after Jochimsen, 1997).

Peaks 5 and 7 were depleted in both the soil and overlying air. Similar degradation profiles were seen in southern ambient air samples from Alabama [34], Texas and Arkansas [38], and in Great Lakes air (Sect. 3.1.3). Their main components, B8-531, B8-806 and B8-809, are predicted to be relatively labile on the basis of molecular structures [39,40]. 

Furthermore, a widely used class of degradable polymers based on acrylate esters are polyamino esters (PAE). These are both efficient gene carriers with an advantageous degradation profile and low cytotoxicity and also easy to synthesize [79, 80] by conjugate addition of either primary or bis(secondary amine)s to different diacrylate esters [81-87]. 

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