Primary nucleation of paracetamol in acetone-water mixtures

The influence of solvent composition on primary nucleation of 4-hydroxyacetanilide (paracetamol) in acetone-water mixtures is investigated. The induction time for primary nucleation is determined, at various degrees of supersaturation and at different temperatures, in different solvent mixture compositions. Supersaturation is generated by the addition of water, and the homogeneous, agitated, isothermal solution is allowed to nucleate. The supersaturation driving force is calculated as the difference in the chemical potential. At equal thermodynamic driving force, the induction time depends on the composition of the solvent mixture. The interfacial energy is in the range 1-3 mJ/m² and tends to increase with decreasing solubility, i.e. increasing water content. The interfacial energy is slightly lower than a value calculated from a contact angle measurement (5 mJ/m²) in pure water and is significantly lower than values predicted by equations derived from simplified theories.