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

ABSTRACT The pressure-temperature ( P – T ) melting curve of lidocaine was determined (d P /d T  = 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.