Isothermal by Design: An Accelerated Approach to thePrediction of the Crystallizability of Slowly Nucleating Systems

A route to the accelerated nucleation of α-para-aminobenzoic acid (pABA) in ethanol:water (EtOH:H2O) mixed solvent solutions, using antisolvent crystallisation, is presented. An ‘isothermal by design’ approach is adopted, whereby the exothermic enthalpy of mixing associated with antisolvent addition is offset by the control of the temperature of the antisolvent added. Induction times (τ) are found to be reduced by over three orders of magnitude using this methodology, consistent with the use of this approach as a nucleation acceleration technique. Calculation of the nucleation kinetic parameters for a range of solution concentrations, compositions and supersaturations (S) reveal that effective interfacial tensions (γ_eff) varies from 8.4 to 2.3 mJ m-2 from solutions in H2O solvent and EtOH solvent, respectively, in line with the trend in solubility. The critical nucleus radius (r*) is calculated to decrease from 1.98 nm to 0.40 nm associated with a decrease in the number of molecules in the critical nucle...