Supersaturation effects in drug development Solubility-enhancing excipients and biorelevant media
Experimental methods are described for measuring solubility and supersaturation of ionisable drugs by potentiometric titration. Characteristic properties are described for compounds that do and do not supersaturate. Graphic examples are shown of the variation of neutral species concentration vs. time during the precipitation of imipramine, dipyridamole and piroxicam from aqueous solution, and of metoclopramine in the presence of PVP and taurocholate. The graphs illustrate how the neutral species may be held in solution at concentrations greater than the equilibrium solubility for extended times, that differ according to the solid state form and the effect of additives.