Effects of Changes in Solubility

Secondary reactions, like crosslinking and gelation, result in precipitations from solution. The extent of the reactions, however, is not necessarily limited, because diffusions of low molecular weight species are still possible. Isolation of useful products, however, often becomes very difficult. 

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An increase in alveolar ventilation will cause an increase in the alveolar concentration of inhaled agent when semi-closed or open breathing circuits are employed. The effect is most noticeable with a highly soluble anaesthetic, such as diethyl ether. With modern, relatively insoluble agents, such as isoflurane and desflurane, the effects of changes in alveolar ventilation are less pronounced. 

Richardson, P. J., D. F. McCafferty, and A. D. V foolfson. 1992. Determination of three-component partial solubility parameters for temazepam and the effects of change in partial molal volume on the thermodynamics of drug solubility J. Pharm. 78 189-198. 

The systems described above are by deLnition metastable and are affected by temperature Luc-tuations. Two other factors inLuencing solubility are the effect of change in crystal morphology and the creation of a higher-energy surface on particles by mechanical stress (grinding). 

The sulfones, sulfolane and 3-methylsulfolane, are shown to function quite well, as cosurfactants with CTAB, in the solubilization of both organophosphorus esters and betahalosulfides. For the organophosphate used, tributylphosphate, it is shown through pseudo-three-component phase diagrams that the sulfone functions as effectively as the alcohol in its role of cosurfactant. Solubilization of chloroethyl ethyl sulfide is less effective when the sulfone cosurfactant is used, but is still a dramatic enhancement over its solubility in water alone. The effect of added salt on the solubilization is reported, as well as the effect of changes in the surfactant-cosurfactant ratio. Preliminary quasielastic lightscattering measurements are also reported for these unconventional systems. 

Base stock specifications, as defined by the producer or the purchaser, largely enumerate the physical properties required for the fluid—typically density, viscosity at two temperatures, viscosity index (VI), low temperature performance measures, flash and volatility properties, and solubility information from aniline point or viscosity-gravity constant (VGC)—the latter two are usually for naphthenic base stocks. While chemical composition is responsible for physical properties, it usually only surfaces as measurements of heteroatom content—sulfur and nitrogen—and aromatics content (or conversely that of saturates). Sulfur and aromatics levels in paraffinic base stocks are now criteria for American Petroleum Institute (API) classifications. However, detailed chemical compositional information is needed to understand the chemistry of the unit processes, the effects of changes in feeds, catalysts, and operating conditions, and behaviors of finished lubricant products. 

Phenytoin is the prototype and most commonly prescribed member of the hydantoin family of drugs. Bioequivalency is a problem with the hydantoins because of their very poor water solubility ( 32 mg/L) and a low therapeutic ratio. Phenytoin exhibits nonlinear pharmacokinetics that exaggerate the effects of changes in the fraction of dose absorbed. Its apparent pKa is in the range of 8.06 to 8.33 and, thus, can form a water-soluble sodium salt ( 15 mg/mL at solution pH >11). ... 

Determination of the dependence of 4 on exposure time would then suffice for a prediction of the change in water sorption with degradation. The effects of changes in temperature and in relative humidity also can be predicted by incorporating the functional dependence of solubility on those parameters, as discussed below, into the expression above. This method can be expected to hold with reasonable validity up to moderate extents of degradation beyond which other changes in physical properties would become overwhelming considerations. 

The soluble fraction was also used to characterize the Epon 828/ A networks (Table III). The presence of a soluble fraction in the off-stoichiometric networks is an indication of topological variations introduced into these networks along with the intended M<3 variations. It will be shown that topology can greatly influence the fracture behavior of these networks, thereby complicating the effects of changes in Me. 

R. A. King, J. D. A. Miller, and D. S. Wakerley, Corrosion of mild steel in cultures of sulphate reducing bacteria effect of changing the soluble iron concentration during growth, Br. Corros. J. S 89-93 (1973). 

Paine et al. [85] extensively studied the effect of solvent in the dispersion polymerization of styrene in the polar media. In their study, the dispersion polymerization of styrene was carried out by changing the dispersion medium. They used hydroxypropyl cellulose (HPC) as the stabilizer and its concentration was fixed to 1.5% within a series of -alcohols tried as the dispersion media. The particle size increased from only 2.0 /itm in methanol to about 8.3 /itm in pentanol, and then decreased back to 1 ixm in octadecanol. The particle size values plotted against the Hansen solubility parameters... 

As indicated, the ionized form of a drug will be more soluble than the nonionized form in the aqueous fluids of the GIT. The classic studies on the beneficial effects of changing nonionized drugs into salt forms were reported by Nelson for tetracycline [25], and Nelson et al. for tolbutamide [26]. Table 2 combines portions of the data from each study. Urinary excretion of the drug or its metabolite was taken as the in vivo measure of the relative absorption rate for the salt and the nonionized... 

Studies of polymorphs in recent years have pointed out the effects of polymorphism on solubility and, more specifically, on dissolution rates. The aspect of polymorphism that is of particular concern to the parenteral formulator is physical stability of the product [8]. Substances that form polymorphs must be evaluated so that the form used is stable in a particular solvent system. Physical stresses that occur during suspension manufacture may also give rise to changes in crystal form [9]. 

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