Highly soluble compounds

Two independent routes to magnesium amidinates containing very bulky terphenyl substituents have been developed, yielding both mono- and bis(amidinate) magnesium complexes. As shown in Scheme 17, the free amidine reacted cleanly with 0.5 equivalents of dibutylmagnesium in toluene to form the bis (amidinate) in moderate yield. The highly soluble compounds was recrystallized from hexanes as clear, colorless crystalline blocks. ... 

The preparation of salts of organic compounds is one of the most important tools available to the for-mulator. Compounds for both IM and IV solutions may require high solubility in order for the drug to be incorporated into acceptable volumes for bolus administration (see Table 1). Sodium and potassium salts of weak acids and hydrochloride and sulfate salts of weak bases are widely used in parenterals requiring highly soluble compounds, based on their overall safety and history of clinical acceptance. 

Fig. 15.5. The biopharmaceutics classification system (BCS). Drug-like molecules are grouped into four BCS classes based on their solubility and permeability. A drug is regarded as a highly soluble compound if the maximum dose given orally is soluble in 250 mL fluid in the...

Fig. 17.3. Experimental versus calculated solubility from VolSurf model. Lower left part, poor solubility central part, medium solubility upper right part, high-solubility compounds.

The correlation was made using PLS analysis within the VolSurf software. The solubility was quantified via the —log[Soly]-values, where Soly was expressed in mol L 1 at 25°C. The quantitative PLS analysis resulted in a two-component model. The recalculated versus experimental PLS plot (Fig. 17.3) shows the correlation obtained. From the objects pattern, a differentiation between very poorly/ poorly/medium/highly/very highly soluble compounds was seen to be possible, though fine quantitative predictions were difficult to achieve. 

A tanker truck carrying a highly soluble compound in Mississippi tried to avoid an armadillo at night, ran off the interstate at a high speed, turned over in the drainage... 

Solubility plays a critical role in the absorption of a drug. A compound with poor solubility may not achieve high enough levels in the stomach and intestine to be absorbed well. However, it is generally true that highly soluble compounds lack sufficient lipophilicity to cross the blood-brain barrier and so, if the compound is an intended CNS drug, a balance must be maintained see Amidon et al. (1995). 

Table 10.2 Percentage of the compounds predicted by the discriminative models for solubility in a mixture of 2% DMSO in water. (High soluble compound, high-medium intermediate to high solubility compounds, medium-low intermediate to low solubility compounds, low considered as insoluble compounds.)...

Atmospheric fate Cresols are not expected to persist in the atmosphere because (1) cresols have low estimated half-lives (less than 1 day) (2) they are sensitive to photolysis and (3) the water solubility of cresols may cause transport of cresols from the atmosphere to the soil or aqueous environment. The photodegradation half-life of cresol isomers during the daytime is 8-10 h while at night it is 2 min. Daytime half-lives would be reduced under smog conditions. Cresols are highly soluble compounds, and gas scavenging will be an efficient removal process as is reflected by high concentrations in rain. 

Figure 10.10 Aqueous solubility (SJ versus octanol-water partition coefficient (/fow) foi" a variety of organic solutes. Note that highly soluble compounds are poorly sorbed and vice versa. Reprinted with permission from Chiou et al. Envir. Sci. Technol. 11 475-477. Copyright 1977 American Chemical Society.

Both dimethyl sulfoxide (CH3S(0)CH3) and dimethyl sulfone (CH3S(02)CH3) are known to rapidly react with OH (which leads to effective further oxidation), and in the presence of liquid water to be very likely removed by absorption in the liquid phase. The effective absorption of dimethyl sulfoxide and dimethyl sulfone in water is due to their high solubility the Henri constant is > 5 10" for both organic sulfoxides. Therefore, effective DMS removal from air can be provided not only by its complete oxidation to CO2, H2O, and SO2, but also by means of formation of highly soluble compounds following scrubbing. Such a no-by-product approach to VOC removal in the wet pulse corona will be considered later in Section 11.8. 

The design of enzymatic reactors for the degradation of highly soluble compounds may consider the use of a semi permeable membrane for the separation of the enzyme and products or substrates (enzyme membrane reactors) or the immobilization of the enzyme in a support (immobilized enzyme reactors). 

Two different reactor configurations were studied in order to evaluate the removal of a highly soluble compound, the azo dye Orange II and a poorly soluble compound, the polycyclic aromatic hydrocarbon (PAH), anthracene. 

Precautions should be taken for low soluble (<0.01 mg/mL) and highly soluble compounds (>0.2 mg/mL). For the former, kinetic solubility... 

As a rule, one should keep DMSO within 1% to 2% to avoid interferences due to the presence of the solvent. Highly soluble compounds can be underestimated when a short incubation time was used between mixing and reading. On the other hand, longer incubation time favors adsorption, thus leading to overestimation of solubility. 

Titanium has a tendency to accumulate in tissues. The concentrations can be very high, as indicated in Table 9.5. Titanium was not excreted in the urine of hamsters injected with metal salts (Merritt et al, 1992). Small concentrations were found in the serum, red blood cells and organs. Only 5.5% of the injected titanium was found in the kidneys, liver, lung and spleen tissues. The authors suggest that titanium accumulates at the injection site due to the high stability of the titanium dioxide that is formed at physiological conditions. In the same study nearly all the injected vanadium was recovered in the urine. This behaviour is similar to that of nickel and cobalt, and is related to the formation of highly soluble compounds. 

Crospovidone (Polyplasdone XL) swells sparingly in water. Its mechanism of action is based on capillary forces, which allow for fast penetration of water into the tablet. In tablets with a high content of highly soluble compounds, such as anhydrous beta-lactose, it is more effective than both other super-disintegrating agents. 

The relative increase in pressure is highest for the compound with the lowest vapor pressure, hence the relative increase in saturation solubility will be highest for poorly soluble compounds when compared to highly soluble compounds. 

Heavy metals precipitation Evaporative crystallization Figure 16.6 Effect of underestimated traces of highly soluble compounds. 

At the other end of the solubility scale are the highly soluble compounds such as the simple salts. In some respect, these materials provide different opportunities as they can be encapsulated before being combined in a paint film. In the case of the rupture of the capsule delivery system, a high initial dose will be supplied to address corrosion but no ongoing dose will be delivered. 

Repeated equilibration with a highly soluble compound containing as much easily exchangeable hydrogen as possible, e.g., ammonia gas or ammonium chloride (Smith and Wojciechowski, 1935). This is a somewhat tedious and wasteful method. 

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