complexes part8

Solubility method
According to the solubility method, excess quantities of the drug are placed in well-stoppered containers, together with a solution of the complexing agent in various concentrations, and the bottles are agitated in a constant-temperature bath until equilibrium is attained. Aliquot portions of the super¬natant liquid are removed and analyzed.
The solubility method was used to inves¬tigate the complexation of p-aminobenzoic acid (PABA) by caffeine. The results are plotted in Figure 11-12. The point A at which the line crosses the vertical axis is the solubility of the drug in water. With the addition of caffeine, the solubility of p-aminobenzoic acid rises linearly owing to complexa¬tion. At point B, the solution is saturated with respect to the complex and to the drug itself. The complex continues to form and to precipitate from the saturated system as more caffeine is added. At point C, all the excess solid PABA has passed into solution and has been converted to the complex. Although the solid drug is exhausted and the solution is no longer saturated, some of the PABA remains uncomplexed in solution, and it combines further with caffeine to form higher complexes such as (PABA-2 caffeine) as shown by the curve at the right of the diagram
The concentration of caffeine and the free, undissolved solid PABA in the plateau region is found to be 1.8 ×10–2 mole/liter, and the Stoichiometric ratio is
 The complex formation is therefore written
 and the stability constant for this 1:1 complex is
 K may be computed as follows. The concentration of the complex [PABA-Caffeine] is equal to the total acid concentration at satura¬tion less the solubility [PABA] of the acid in water. The concentration [Caffeine] in the solution at equilibrium is equal to the caffeine added to the system less the concentration that has been converted to the complex. The total acid concentration of saturation is 4.58×10–2 mole/liter when no caffeine is added (solubility of PABA), and is 5.312 x 10–2 mole/liter when 1.00 x 10–2 mole/liter of caffeine is added.