Ternary Co-Crystal Phase Diagrams of Benzoic/4-Aminobenzoic Acid + Isoniazid + Ethanol/Acetonitrile at Several Temperatures

At 298.15, 308.15, and 318.15 K, mutual solubility was experimentally measured under about 0.1 MPa for four systems: benzoic acid + isoniazid + ethanol, 4-aminobenzoic acid + isoniazid + ethanol, benzoic acid + isoniazid + acetonitrile, and 4-aminobenzoic acid + isoniazid + acetonitrile. The measured mutual solubility of these systems was used to generate isothermal cocrystal phase diagrams. An approach of Schreinemaker’s wet residue together with XRD scans was utilized to ratify the solids appeared in these systems, which pertained to isoniazid, 4-aminobenzoic acid, and 2:1 4-aminobenzoic acid-isoniazid cocrystal (mole ratio) for 4-aminobenzoic acid + isoniazid + ethanol/acetonitrile systems and isoniazid, benzoic acid, and 1:1 benzoic acid-isoniazid cocrystal (mole ratio) for benzoic acid + isoniazid + ethanol/acetonitrile systems. There were three cosaturated curves, five crystalline regions, and two cosaturated points in the ternary benzoic acid + isoniazid + ethanol/acetonitrile and 4-aminobenzoic acid + isoniazid + ethanol/acetonitrile systems, respectively. Additionally, using molecular simulation, the hydrogen bond and interaction energy between isoniazid and benzoic acid/4-aminobenzoic acid were discussed.