Thomas Lafitte, Vasileios Papaioannou, Simon Dufal, and Constantinos C. Pantelides

Process Systems Enterprise Ltd., London, UK


A large proportion of active pharmaceutical ingredients (APIs) are produced and administered in the solid form. As a result, the thermodynamic equilibrium of systems involving solid and liquid phases is of central importance to API manufacturing where unit operations such as crystallization, particularly in organic solvents, play a prominent role in the separation and purification of APIs and their intermediates during chemical synthesis. Equilibrium compositions determine the driving forces for crystal formation and growth, and are important factors for the selection of an appropriate solvent for each separation step.

Solid–liquid equilibrium in aqueous environments also plays a central role in the oral absorption of pharmaceuticals [1], this time in determining the driving forces for dissolution of solid APIs in the lower gastrointestinal (GI) tract, consequently affecting drug bioavailability, particularly in the case of very low solubility drugs. The variation of pH along the GI tract and the presence of a variety of ions may also cause the reprecipitation of the API in various forms (e.g. salts) at different sections of the GI tract, which may have an inhibitory effect on bioavailability.

Recent years have witnessed a significant increase in the use of ...

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