Liquid-Liquid Miscibility Gaps and Hydrate Formation in Drug-Water Binary Systems: Pressure-Temperature Phase Diagram of Lidocaine and Pressure-Temperature-Composition Phase Diagram of the Lidocaine-Water System

The pressure-temperature (P-T) melting curve of lidocaine was determined (dP/dT = 3.56 MPa K− 1), and the lidocaine-water system was investigated as a function of temperature and pressure. The lidocaine-water system exhibits a monotectic equilibrium at 321 K (ordinary pressure) whose temperature increases as the pressure increases until the two liquids become miscible. A hydrate, unstable at ordinary pressure, was shown to form, on increasing the pressure, from about 70 MPa at low temperatures (200-300 K). The thermodynamic conditions of its stability were inferred from the location of the three-phase equilibria involving the hydrate in the lidocaine-water pressure-temperature-mole fraction (P-T-x) diagram.