Effect of pH on Solubility

In discussing solubility, we have assumed that the only equilibrium of interest was the one between the sohd ionic compound and its ions in solution. Sometimes, however, it is necessary to account for other reactions the ions might undergo. For example, if the anion is the conjugate base of a weak acid, the anion reacts with HsO ion. You should expect the solubility to be affected by pH. We will look into this possibility now. 

Consider the equilibrium between solid calcium oxalate, CaC204, and its ions in aqueous solution  

Because the oxalate ion is conjugate to a weak acid (hydrogen oxalate ion, HC2O4 ), you would expect it to react with any H30 ion that is added—say, from a strong acid  

According to Le Chatelier s principle, as C20/ ion is removed by reaction with H30 ion, more calcium oxalate dissolves to replenish some of the C20/ ion. 

Therefore, you expect calcium oxalate to be more soluble in acidic solution (low pH) than in pure water. 

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Another important parameter that may affect a precipitate s solubility is the pH of the solution in which the precipitate forms. For example, hydroxide precipitates, such as Fe(OH)3, are more soluble at lower pH levels at which the concentration of OH is small. The effect of pH on solubility is not limited to hydroxide precipitates, but also affects precipitates containing basic or acidic ions. The solubility of Ca3(P04)2 is pH-dependent because phosphate is a weak base. The following four reactions, therefore, govern the solubility of Ca3(P04)2. 

An important example of the effect of pH on solubility is tooth decay. Tooth enamel contains the mineral hydroxyapatite, which is insoluble near neutral pH, but dissolves in acid because both phosphate and hydroxide in the hydroxyapatite react with H+ ... 

The effect of pH on solubility is also important in understanding how fluoride ion reduces tooth decay. When tooth enamel comes in contact with F ions in drinking water or fluoride-containing toothpaste, OH- ions in hydroxyapatite, Ca5(PC>4)30H, are replaced by F- ions, giving the mineral fluorapatite, Ca5(PC>4)3F. Because F- is a much weaker base than OH-, Ca5(P04)3F is much more resistant than Cas(P04)30H to dissolving in acids. 

Effect of pH on Solubility The strongly polar hydrogen-bonding properties of water make it an... 

Effect of pH on Solubility. The solubility of many substances is stfongly dependent on the acidity or basicity of the solution in which the substances are dissolved. An ordinary salt of a strong acid and a strong base, such as sodium chloride, is soluble to almost the same extent in an acidic or basic solution (not containing sodium ion or chloride ion) as in pure water. However, the solubility of an acid or a base in a solution which is nor neutral would be expected to be changed because of the common-ion effect. This may be illustrated by the following example. 

The solubilization techniques for injectable formulations are similar to those in oral formulations and include pH adjustment, mixed aqueous/organic cosolvents, organic solvent mixtures, cyclodextrin com-plexation, emulsions, liposomes, polymeric gels, and combinations of techniques. " Molecules that are non-ionizable, lipophilic, and non-polar are challenging to formulate owing to their low water solubility and no effect of pH on solubility. Examples include paclitaxel, docetaxel, cyclosporin A, etoposide, loraze-pam, tacrolimus, testosterone enanthate, and halo-peridol decanoate, and they are all solubilized in non-aqueous solutions composed entirely of organic solvent(s), which are usually but not always diluted prior to administration. 

Some solids are only weakly soluble in water but dissolve readily in acidic solutions. Copper and nickel sulfides from ores, for example, can be brought into solution with strong acids, a fact that aids greatly in the separation and recovery of these valuable metals in their elemental forms. The effect of pH on solubility is shown dramatically in the damage done to buildings and monuments by acid precipitation (Fig. 16.8). Both marble and limestone are made up of small crystals of calcite (CaCOs), which dissolves to only a limited extent in natural rain (with a pH of about 5.6) but dissolves much more extensively as the rainwater becomes more acidic. The reaction... 

One direct effect of pH on solubility occurs with the metal hydroxides. The concentration of OH appears explicitly in the expression for the solubility product of such compounds. Thus, for the dissolution of Zn(OH)2(s),... 

Unfortunately, the predicted values for solubility and those experimentally determined do not always correlate well because the effect of pH on solubility is often complicated by other factors. This was clearly illustrated during a study on the solubility of salts of a poorly soluble and weakly basic experimental antimalarial dmg. The solubility of the DL-lactate salt was shown to be 200 times greater than the hydrochloride (see Table 37.5) and twice that of the L-lactate, suggesting that the OL-lactate could provide a route to a parenteral formulation. 

Many organizations use colon adenocarcinoma (Caco-2) for detailed study of permeability however, this method can be resource intensive. Parallel artificial-membrane permeability (PAMPA) [19] has proven to be a reliable predictor of passive transcellular permeability for intestinal absorption prediction. It is also useful to interpret results of cell-based discovery assays, in which cell-membrane permeability is limiting. Finally, pTf provides insight into the pH dependence of solubility and permeability. It can be measured [20] or calculated to get an understanding of the regions of the intestine in which the compound will be best absorbed, as well as to anticipate the effect of pH on solubility and pemieability. Permeability at the blood-brain barrier (BBB) also can be rapidly profiled [21]. 

Figure 6. Effect of pH on solubility. Key , calculated value and A, experimental data.

Figure 12.8 The effect of pH on solubility (S) of 3-lactoglobulin. The pi of this protein is 5.2. (Data from Gronwell 1942.)...

The effect of pH on solubility of silica at temperatures from 0 to 200 C was measured by Goto (167a) and is shown in Figure 1.7. At 22-100 C the solubility was about 30% higher than for most powders and gels, as shown in Figure 1.7. This is... 

Effect of pH on Solubility 639 Predicting the Formation of a Precipitate 2sp vs. Afsp 639... 

Detailed studies of the effect of pH on solubility of amino acids have been canied out by Hitchcock (103) for tyrosine and by Sano (180) for cystine. The simple relations given by them may readily be generalised so as to apply to a complex molecule such as a protmn with a very large number of ionising groups. 

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