Slow-release portion

FIGURE 40.15 Release profiles of nifedipine from double-layer tablets (25 mg as 5 mg nifedipine) consisting of nifedipine-HP-(3-CyD with 3% HCO-60 as fast-release portion (FRP) and nifedipine-HPC-M as slow-release portion (SRP) in various weight ratios (FRP SRP) in water at 37°C. O, 1 3 , 1 2 A, 1 1 A, 2 1 , 3 1. 

Erodings of Slow-Releasing Core Tablets. The sustained-dose portion of a dmg is granulated with hydrophobic materials such as waxes, fatty acids, or fatty alcohols and compressed into a core. The initial dose is added to the core by a modified sugar coating process or by compression coating. Thus, a tablet within a tablet is created. The core erodes slowly to release the active ingredient. 

Currently, the most advanced form of insulin therapy is the insulin pump, also referred to as continuous subcutaneous insulin infusion (CSII). Using the short- or rapid-acting insulins only, these pumps are programmed to provide a slow release of small amounts of insulin as the basal portion of therapy, and then larger bolus doses are injected by the patient to account for the consumption of food. 

Phthalates are easily released into the environment because there is no covalent bond between them and plastics in which they are mixed. The major portion of phthalates that are found in the environment comes from the slow releases of phthalates from plastics and other phthalate containing articles due to weathering. At natural conditions, phthalates are hydrolyzed to some extent yielding their corresponding monoesters, which are also environmental pollutants [15]. They show poor mobility in soil but aqueous leachates from landfills may contain trace amounts of more soluble products of phthalate degradation [11, 16]. 

A difference in the rate of adsorption and desorption of Cr(VI) by alluvium was also observed in a batch experiment (Fig. 8.44b). On the basis of these two experiments, Stollenwerk and Grove (1985) concluded that the quantity of Cr(VI) adsorbed by alluvium is a function of its concentration as well as of the type and concentration of other anions in solution. The Cr(VI) adsorbed through nonspecific processes is desorbed readily by a Cr-free solution. Stronger bonds that are formed between Cr(VI) and alluvium during specific adsorption result in very slow release of this fraction. The Cr(Vl) desorption from the alluvium material illustrates the hysteresis process that results from chemical transformation of a portion of contaminant retained in the subsurface. 

Desorption kinetic studies were conducted with freshly contaminated soils and aged soils (i.e., soils that were allowed to have extended contact time of 3 months and 5 months during the sorption step). Three levels of contamination were used. To illustrate here, soil desorption kinetics data for 1,3-DCB with silty soil from the PPI site was plotted with the fraction of the contaminant released as a function of time in Fig. 5. Again, the results for other chemicals are not discussed here as the findings are very similar. As shown in Fig. 5, a substantial portion of the contaminant is released within the first 20-30 h, followed by a very slow release over a very long period. This slow release was observed over the entire duration of the experiment (100-450 h). Approximately 60% of 1,3-DCB was desorbed in the first 24 h for freshly contaminated soils. 

Pseudoesters, for example, 221, in which the alcohol portion is a fragrance (such as geraniol), have been developed for the slow release of scent. Alkaline hydrolysis of compound 221 requires time so that the rate at which scent is released is prolonged over that of simple evaporation <2001J(P2)438>. A similar approach involves the preparation of acyclic esters 222 and 223 from phthalide 224 and phthalic anhydride 225, respectively. In this case, the slow release of fragrance is the result of an intramolecular transesterification processes <2003USP20030148901>. 

Nitrogen is present in peat in various forms not well understood. A considerable portion is known to be in the form of protein, but not in a free state. It is complexed with lignin, cellulose and hemicellulose. In such forms it is not readily released as ammonia, but does undergo slow release as the peat decomposes. It is very fortunate that it is not readily released, because in this age of abundant supplies of commercial synthetic ammonia, the nitrogen is far more valuable to agriculture when present as complexes than if present as ammonia. 

Interleukin-1 (IL-1) produced by monocytes and several other cell types [70, 146] has a wide array of biological properties, including T cell activation and inflammatory interactions with muscle, liver, fibroblasts, brain and bone [70, 146], IL-1, both natural and recombinant, has been shown to release histamine from human basophils and from human adenoidal mast cells [70,146,151] and this release was abolished by an IL-1 antibody. However, the average release produced by 10 units of IL-1 was less than 20% and there was considerable variability between populations of basophils in the extent of histamine release. Moreover, the secretory response elicited was quite slow (within 15 min) compared with that of other peptides [151]. Desensitization of the basophils by anti-IgE serum had no effect on the subsequent IL-1 response, suggesting different mechanisms of action [ 151], as has been the case with other peptides. Interestingly, the portion of the IL-1 molecule that is responsible for its immu-nostimulatory activity appears to be separate from that portion responsible for its proinflammatory effects [152]. However, that portion of the molecule responsible for eliciting basophil and mast-cell histamine release has not as yet been defined. 

Clearly, if in equation 4.78 k is very fast and k2 is negligibly slow, the release of P is easily measured and related to the concentration of enzyme. However, in practice, k2 is generally not negligible, so that there is an initial burst of formation of P, followed by a progressive increase as the intermediate turns over. The mathematics of this situation was described previously (equations 4.37 to 4.46). It was shown that the overall release of products is linear with time after an initial transient. From equation 4.46 it can be seen that the linear portion extrapolates back to a burst, ir, given by... 

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