Measurement of Solubilities and Corroboration

There is no single method that is generally the optimal one for all types of systems. The most suitable method for a given system depends on various subjects such as available amount of substance (which is often a limiting factor during early development stages), kind of solvent (e.g., very viscous solvents cause difficulties with stirring or are hard to evaporate), required analytical techniques, or necessity of additional solid-phase characterization. 

1) The measurement of the saturation concentration (Csat) at constant temperature (a) by successively adding known amounts of solid to the solvent until saturation is achieved (addition method) or (b) by equilibrating and analyzing a solution containing an excess of solid (excess method). 

2) The measurement of the saturation (solubility) temperature by heating a solution of known composition with an initial excess of solid until last particles are dissolved. 

The two approaches differ in the temperature regime applied. In case (1), the sample is analyzed at a constant temperature (isothermal technique) in case (2), the sample is subjected to a slow controlled heating (polythermal technique). 

In the following sections, examples of isothermal and polythermal techniques for solubility measurement are presented. Here, advantages and weaknesses of the particular methods as well as the question, how to guaranty equilibrium conditions, are addressed. 

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