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

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 6; pp. 2756 - 2765
• Main Authors: Ceolin, René, Barrio, Maria, Tamarit, Josep-Lluis, Veglio, Nestor, Perrin, Marc-Antoine, Espeau, Philippe
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.06.2010; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Biological and medical sciences; Dosage Forms; General pharmacology; high-pressure differential thermal analysis; Hydroxides; Lidocaine; lidocaine-water binary system; Medical sciences; Oxides; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pressure; pressure-temperature diagrams; pressure-temperature-mole fraction diagrams; stability of molecular hydrates under pressure; Temperature; Thermodynamics; Water - chemistry; stability of molecular hydrates under pressure; high-pressure differential thermal analysis; thermodynamics; pressure–temperature diagrams; lidocaine–water binary system; lidocaine; pressure–temperature–mole fraction diagrams; Water; Drug; Temperature; Stability; Pharmaceutical technology; Phase diagram; Binary system; Anticonvulsant; Antiarrhythmic agent; pressure-temperature-mole fraction diagrams; Pressure; High pressure; Local anesthetic; Thermodynamics; Miscibility; lidocaine-water binary system; Organic amide; Thermal analysis; Lidocaine; Physicochemical properties; pressure-temperature diagrams; Hydrates
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22039

The pressure-temperature (P–T) melting curve of lidocaine was determined (dP/dT=3.56MPaK−1), and the lidocaine–water system was investigated as a function of temperature and pressure. The lidocaine–water system exhibits a monotectic equilibrium at 321K (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 70MPa at low temperatures (200–300K). 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.