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Probenecid (PB), as a pharmacotherapeutic agent for treating gout, confronts challenges associated with heterogeneous particle size distribution and irregular morphology, impacting postprocessing efficiency. Therefore, further investigation of the nucleation behavior of PB is necessary to address these issues. The nucleation behavior of PB in four solvents was investigated using metastable zone width (MSZW) experiments, the Nývlt model, and the modified Sangwal’s theory. The results revealed that the MSZW broadened, and the interfacial energy (γ) and pre-exponential factor (A) increased with higher cooling rates and lower saturation temperatures. As the chemical potential increases, the critical nucleus size (rcrit) and Gibbs free energy (ΔGcrit) decrease. Infrared (FTIR) spectral analysis suggested that the distinct nucleation behavior of PB in various solvents can be attributed to the competition between intermolecular interactions, predominantly hydrogen bonding and dimerization. Radial distribution function (RDF) analysis and solvation energy calculation suggested that the nucleation behavior becomes more difficult as the solute–solvent intermolecular interactions become stronger.

The solubility of N-acetyl-l-leucine in 12 mono organic solvents (methanol, ethanol, n-propanol, 2-propanol, 1-butanol, isobutanol, 2-butanol, methyl acetate, ethyl acetate, propyl acetate, acetone, and acetonitrile) was determined by the gravimetric method over the temperatures ranging from 283.15 to 323.15 K at 0.1 MPa. The solubility of N-acetyl-l-leucine in each experimental solvent increases with increasing temperature. Moreover, the solubility is an order of magnitude higher in alcohol solvents than in other solvents, which is mainly attributed to the hydrogen bond formation. In addition, the experimental solubility data are correlated by three models, including the modified Apelblat equation, λhequation, and the nonrandom two-liquid (NRTL) model. All of the average relative deviation % values are less than 3.72%, which indicates that the three models have satisfactory correlations. Furthermore, the mixing thermodynamic properties of N-acetyl-l-leucine in 12 mono solvents including ΔmixG0, ΔmixH0, and ΔmixS0are calculated based on the NRTL model, indicating that the mixing process was spontaneous.