Solubility weak acid salts

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. 

Kp values may be found in the literature or they may be calculated from AG° values of the weak acid anion and the weak acid. Salts can be formed between cations and the A1(0H)4 anion, these being called tetrahydrox-oaluminates. Those of the alkali metals are soluble, but most others are insoluble. 

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. 

The absorption of orally administered solids is slow, and exponential. The solution rate is proportional to the drug s surface area, and the availability for absorption decreases in the order solutions, suspensions, capsules, compressed tablets, coated tablets. Sodium salts of poorly soluble weak acids usually produce higher blood-levels than the free acids, because the hydrochloric acid of the gastric juice liberates the weak acid from its salt in a much finer form than any in which it can be marketed. The kinetics of dissolving drugs is reviewed by Wagner (1961). 

Specific examples of important equilibrium systems include sparingly soluble salts, weak acids, and weak bases. For salts, the solubility product constant, K, provides a way to calculate equilibrium concentrations and molar solubilities. Weak acids and bases also have specifically named equilibrium constants the acid ionization constant, and the base ionization constant, Aj,. 

The following calculations were then done using ternary weak acid - salt water solubility data in which the solution is saturated with the weak electrolyte to get the activity coefficient of the undissociated portion of the weak acid ... 

The solution will then contain the free acid and the hydrochloride of the base either of these may separate if sparingly soluble. If a sohd crystallises from the cold solution, filter, test with sodium bicarbonate solution compare Section 111,85, (i) and compare the m.p. with that of the original compound. If it is a hydrolysis product, examine it separately. Otherwise, render the filtrate alkahne with sodium hydroxide solution and extract the base with ether if the presence of the unchanged acyl canpound is suspected, extract the base with weak acid. Identify the base in the usual manner (see Section IV, 100). The acid will be present as the sodium salt in the alkaline extract and may be identified as described in Section IV,175. 

Iron Reduction. The reduction of nitrophenols with iron filings or turnings takes place in weakly acidic solution or suspension (30). The aminophenol formed is converted to the water soluble sodium aminopheno1 ate by adding sodium hydroxide before the iron-iron oxide sludge is separated from the reaction mixture (31). Adjustment of the solution pH leads to the precipitation of aminophenols, a procedure performed in the absence of air because the salts are very susceptible to oxidation in aqueous solution. 

The characteristics of soluble sihcates relevant to various uses include the pH behavior of solutions, the rate of water loss from films, and dried film strength. The pH values of sihcate solutions are a function of composition and concentration. These solutions are alkaline, being composed of a salt of a strong base and a weak acid. The solutions exhibit up to twice the buffering action of other alkaline chemicals, eg, phosphate. An approximately linear empirical relationship exists between the modulus of sodium sihcate and the maximum solution pH for ratios of 2.0 to 4.0. 

The most common method of purification of inorganic species is by recrystallisation, usually from water. However, especially with salts of weak acids or of cations other than the alkaline and alkaline earth metals, care must be taken to minimise the effect of hydrolysis. This can be achieved, for example, by recrystallising acetates in the presence of dilute acetic acid. Nevertheless, there are many inorganic chemicals that are too insoluble or are hydrolysed by water so that no general purification method can be given. It is convenient that many inorganic substances have large temperature coefficients for their solubility in water, but in other cases recrystallisation is still possible by partial solvent evaporation. 

In seawater, HCO3 ions lead to surface films and increased polarization. In aqueous solutions low in salt and with low loading of the anodes, less easily soluble basic zinc chloride [10] and other basic salts of low solubility are formed. In impure waters, phosphates can also be present and can form ZnNH4P04, which is very insoluble [11]. These compounds are only precipitated in a relatively narrow range around pH 7. In weakly acid media due to hydrolysis at the working anode, the solubility increases considerably and the anode remains active, particularly in flowing and salt-rich media. 

Compounds of Tl have many similarities to those of the alkali metals TIOH is very soluble and is a strong base TI2CO3 is also soluble and resembles the corresponding Na and K compounds Tl forms colourless, well-crystallized salts of many oxoacids, and these tend to be anhydrous like those of the similarly sized Rb and Cs Tl salts of weak acids have a basic reaction in aqueous solution as a result of hydrolysis Tl forms polysulfldes (e.g. TI2S3) and polyiodides, etc. In other respects Tl resembles the more highly polarizing ion Ag+, e.g. in the colour and insolubility of its chromate, sulfide, arsenate and halides (except F), though it does not form ammine complexes in aqueous solution and its azide is not explosive. 

For sparingly soluble salts of a strong acid the effect of the addition of an acid will be similar to that of any other indifferent electrolyte but if the sparingly soluble salt MA is the salt of a weak acid HA, then acids will, in general, have a solvent effect upon it. If hydrochloric acid is added to an aqueous suspension of such a salt, the following equilibrium will be established ... 

With the salts of certain weak acids, such as carbonic, sulphurous, and nitrous acids, an additional factor contributing to the increased solubility is the actual disappearance of the acid from solution either spontaneously, or on gentle warming. An explanation is thus provided for the well-known solubility of the sparingly soluble sulphites, carbonates, oxalates, phosphates(V), arsenites(III), arsenates(V), cyanides (with the exception of silver cyanide, which is actually a salt of the strong acid H[Ag(CN)2]), fluorides, acetates, and salts of other organic acids in strong acids. 

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 ... 

Because the concentrations of ions in a solution of a sparingly soluble salt are low, we assume, just as we did for solutions of weak acids and bases (Section 10.7), that we can approximate Ksp by... 

Before leaving the subject of polarity and in relation to uptake and distribution, mention should be made of weak acids and bases. The complicating factor here is that they exist in solution in different forms, the balance between which is dependent on pH. The different forms have different polarities, and thus different values. In other words, the values measured are pH-dependent. Take, for example, the plant growth regulator herbicide 2,4-D. This is often formulated as the sodium or potassium salt, which has high water solubility. When dissolved in water, however, the following equilibrium is established ... 

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. 

An aqueous solution of a soluble salt contains cations and anions. These ions often have acid-base properties. Anions that are conjugate bases of weak acids make a solution basic. For example, sodium fluoride dissolves in water to give Na, F, and H2 O as major species. The fluoride anion is the conjugate base of the weak acid HF. This anion establishes a proton transfer equilibrium with water ... 

Nitrite is an extremely reactive chemical and is soluble in the aqueous phase of meat. It is usually used for curing in the form of the sodium salt. The nitrite ion is the conjugate base of nitrous acid (a weak acid) and has a PK of 3.36. The usually mild acid conditions found in meat give formation of only a small quantity of nitrous acid when nitrite is added to the meat ( ) ... 

Separations based upon differences in the chemical properties of the components. Thus a mixture of toluene and aniline may be separated by extraction with dilute hydrochloric acid the aniline passes into the aqueous layer in the form of the salt, aniline hydrochloride, and may be recovered by neutralisation. Similarly, a mixture of phenol and toluene may be separated by treatment with dilute sodium hydroxide. The above examples are, of course, simple apphcations of the fact that the various components fall into different solubility groups (compare Section XI,5). Another example is the separation of a mixture of di-n-butyl ether and chlorobenzene concentrated sulphuric acid dissolves only the n-butyl other and it may be recovered from solution by dilution with water. With some classes of compounds, e.g., unsaturated com-poimds, concentrated sulphuric acid leads to polymerisation, sulphona-tion, etc., so that the original component cannot be recovered unchanged this solvent, therefore, possesses hmited apph cation. Phenols may be separated from acids (for example, o-cresol from benzoic acid) by a c ute solution of sodium bicarbonate the weakly acidic phenols (and also enols) are not converted into salts by this reagent and may be removed by ether extraction or by other means the acids pass into solution as the sodium salts and may be recovered after acidification. Aldehydes, e.g., benzaldehyde, may be separated from liquid hydrocarbons and other neutral, water-insoluble liquid compounds by shal g with a solution of sodium bisulphite the iddehyde forms a solid bisulphite compound, which may be filtered off and decomposed with dilute acid or with sodium bicarbonate solution in order to recover the aldehyde. 

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. 

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