Solubility weak base salts

Figure 4.1 shows that the solubility is a maximum at pH ,ax- This occurs because, at this pH, the solution is saturated in both the weak base salt species and the neutral species that is, the solubility is controlled by both the solubility product and the neutral species intrinsic solubility. According to Equation (4.17) an increase in cation concentration gives an increase in the pH of maximum solubility (a decrease in H ax ). 

Many drug substances fall in the category of slightly soluble weak acids, or slightly soluble weak bases, whose salt forms are much more soluble in water. Upon addition of acid to an aqueous solution of a soluble salt of a weak acid, or upon addition of alkali to an aqueous solution of a soluble salt of a weak base, crystals often result. These crystals may be different from those obtained by solvent crystallization of the weak acid or weak base. Nucleation does not necessarily commence as soon as the reactants are mixed, unless the level of supersaturation is high, and the mixing stage may be followed by an appreciable time lag before the first crystals can be detected. Well-formed crystals are more likely to result in these instances than when rapid precipitation occurs. 

Originally, general methods of separation were based on small differences in the solubilities of their salts, for examples the nitrates, and a laborious series of fractional crystallisations had to be carried out to obtain the pure salts. In a few cases, individual lanthanides could be separated because they yielded oxidation states other than three. Thus the commonest lanthanide, cerium, exhibits oxidation states of h-3 and -t-4 hence oxidation of a mixture of lanthanide salts in alkaline solution with chlorine yields the soluble chlorates(I) of all the -1-3 lanthanides (which are not oxidised) but gives a precipitate of cerium(IV) hydroxide, Ce(OH)4, since this is too weak a base to form a chlorate(I). In some cases also, preferential reduction to the metal by sodium amalgam could be used to separate out individual lanthanides. 

Group II. The classes 1 to 5 are usually soluble in dilute alkali and acid. Useful information may, however, be obtained by examining the behaviour of Sails to alkaline or acidic solvents. With a salt of a water-soluble base, the characteristic odour of an amine is usually apparent when it is treated with dilute alkali likewise, the salt of a water soluble, weak acid is decomposed by dilute hydrochloric acid or by concentrated sulphuric acid. The water-soluble salt of a water-insoluble acid or base will give a precipitate of either the free acid or the free base when treated with dilute acid or dilute alkali. The salts of sulphonic acids and of quaternary bases (R4NOH) are unaflFected by dilute sodium hydroxide or hydrochloric acid. 

Diaziridines are weak bases, They can be extracted from organic solvents with aqueous mineral acids. With increasing number and chain length of alkyl substituents the solubility in aqueous mineral acids decreases. l-MethyI-2-n-butyl-3-hexyldiaziridine is soluble only in concentrated hydrochloric acid. Stable oxalates can in some cases be prepared from 1-aIkyI-diaziridines (43). The salts are stable indefinitely and by the action of alkali the diaziridines can be recovered. Diaziridines dialkylated on nitrogen (44) are hardly capable of salt... 

Solutions which prevent the hydrolysis of salts of weak acids and bases. If the precipitate is a salt of weak acid and is slightly soluble it may exhibit a tendency to hydrolyse, and the soluble product of hydrolysis will be a base the wash liquid must therefore be basic. Thus Mg(NH4)P04 may hydrolyse appreciably to give the hydrogenphosphate ion HPO and hydroxide ion, and should accordingly be washed with dilute aqueous ammonia. If salts of weak bases, such as hydrated iron(III), chromium(III), or aluminium ion, are to be separated from a precipitate, e.g. silica, by washing with water, the salts may be hydrolysed and their insoluble basic salts or hydroxides may be produced together with an acid ... 

C16-0105. Write the equilibrium reaction and equilibrium constant expression for each of the following processes (a) Trimethylamine, (CH3)3 N, a weak base, is added to water, (b) Hydrofluoric acid, HF, a weak acid, is added to water, (c) Solid calcium sulfate, CaSOq, a sparingly soluble salt, is added to water. 

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. 

Figure 6.8 shows the Bjerrum plots for an weak acid (benzoic acid, pKa 3.98, log So — 1.55, log mol/L [474]), a weak base (benzydamine, pKa 9.26, log So —3.83, log mol/L [472]), and an ampholyte (acyclovir, pKa 2.34 and 9.23, log So — 2.16, log mol/L I/40N ). These plots reveal the pKa and pA pp values as the pcH values at half-integral % positions. By simple inspection of the dashed curves in Fig. 6.8, the pKa values of the benzoic acid, benzydamine, and acyclovir are 4.0, 9.3, and (2.3, 9.2), respectively. The pA pp values depend on the concentrations used, as is evident in Fig. 6.8. It would not have been possible to deduce the constants by simple inspection of the titration curves (pH vs. volume of titrant, as in Fig. 6.7). The difference between pKa and pA pp can be used to determine log So, the intrinsic solubility, or log Ksp, the solubility product of the salt, as will be shown below.

Buffer solutions are produced by mixing together solutions of a weak acid and its soluble, ionic salt or a weak base and its soluble, ionic salt in approximately the same concentrations. The concentration of one can be no more than ten times the concentration of the other. 

Strontium acetate is neither a weak acid nor a weak base—it is a salt. As a soluble salt, it is a strong electrolyte and it will dissociate as follows ... 

The unequal basicities of the three nitranilines can be illustrated by the following experiment. It is a general property of the salts of weak bases—as well as of weak acids—that in aqueous solution they are stable only if an excess of acid (or alkali) is present. When such solutions are diluted with water hydrolysis occurs as a result of the operation of the law of mass action. In the present case this phenomenon shows itself in the appearance of the yellow colour characteristic of the bases and finally, since the nitranilines are sparingly soluble in water, in their precipitation in crystalline form. The weaker the base the smaller is the amount of water which must be added in order to make the hydrolysis perceptible. 

Sparingly soluble salts of primary aromatic amines are diazotised in suspension, with vigorous stirring. Very weak bases such as halo-genated anilines and nitroanilines require a large excess of acid for salt formation they are first dissolved in just sufficient hot concentrated hydrochloric acid, which is then simultaneously cooled in ice and diluted. In this way the salts, which are mostly sparingly soluble, are precipitated in a finely divided condition. Dissolution in concentrated sulphuric acid and direct diazotisation of the sulphate, precipitated as a fine powder by means of ice, is often to be recommended. The free amines, however, should never be diazotised in acid suspension because they react far too slowly. Salt formation should first be ensured. 

Soluble salts of strong acids and weak bases... 

Local anesthetics are weak bases and are usually made available clinically as salts to increase solubility and stability. In the body, they exist either as the uncharged base or as a cation. The relative proportions of these two forms is governed by their pKa and the pH of the body fluids according to the Henderson-Hasselbalch equation ... 

C. Sulfamates prepared from weak bases form acidic solutions, whereas those prepared from strong bases produce neutral solutions. The pH of 5 wt % solution of ammonium sulfamate is 5.2. Crystals of ammonium sulfamate deliquesce at relative humidity of 70% and higher. Both ammonium sulfamate [7773-06-0] and potassium sulfamate [13823-30-2] hbemte ammonia at elevated temperatures and form the corresponding imidodisulfonate (12). Inorganic sulfamates are quite water-soluble, except for the basic mercury salt. Some relative solubilities of sulfamates at 25°C in 100 g of water are ammonium, 103 g sodium, 106 g magnesium, 119 g calcium, 67 g barium, 34.2 g zinc, 115 g and lead, 218 g. The properties of a number of sulfamates may be found in the literature (see Table 5). 

Weak base and a soluble salt containing the conjugate acid of the weak base... 

Hydrolysis.—A salt that contains as one of its constituents either a weak acid or a weak base will not dissolve in water to form a neutral solution. Water acts upon such a salt partially to reverse the reaction of neutralization, liberating equivalent parts of both acid and base. To obtain in solid form a normal salt that is subject to hydrolysis, it is necessary to have present in the solution considerable excess of either the acid or the base, depending upon the nature of the salt and the mother liquor from which the salt is crystallized will contain this excess. When the crystals have been drained from this mother liquor, they cannot be washed with the pure solvent, for this would leave them coated with a film of the aqueous solution of the normal salt, which would then undergo hydrolysis. If either the acid or the base of which the salt is composed should be difficultly soluble,... 

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