Solubility diagram general procedure

Herriott (1957) has reviewed the use of the solubility diagram as a tool for detecting the presence of impurities in soluble substances, particularly proteins. In these days of advanced types of instrumentation and sophisticated methods, it is worth recalling the use of a method that depends on solubility principles and is not difficult to apply. The method is based on application of the phase rule, but one need not apply the phase rule or even understand it to determine whether a preparation contains one or more components. Herriott has discussed the general procedure, the interpretation of results, the quantitative limitations of the method, the conditions and details of technique, and the separation of protein components by methods based on the solubility diagram. 

The maximum additive concentration (MAC) is defined as the maximum amount of solubilisate, at a given concentration of surfactant, that produces a clear solution. Different amounts of solubilisates, in ascending order, are added to a series of vials containing the known concentration of surfactant and mixed until equilibrium is reached. The maximum concentration of solubilisate that forms a clear solution is then determined visually. This same procedure can be repeated for the different concentrations of surfactant in a known amount of solubilisate in order to determine the optimum concentration of surfactant (Figure 4.24). Based on this information, one can construct a ternary phase diagram that describes the effects of three constituents (i.e., solubilisate, surfactant, and water) on the micelle system. Note that unwanted phase transitions can be avoided by ignoring the formulation compositions near the boundary. In general, the MAC increases with an increase in temperature. This may be due to the combination of the increase of solubilisate solubility in the aqueous phase and the micellar phase rather than an increased solubilization by the micelles alone. 

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