Dimorphism of the prodrug l-tyrosine ethyl ester: Pressure–temperature state diagram and crystal structure of phase II

✍ Scribed by Ivo B. Rietveld; Maria Barrio; Josep-Lluís Tamarit; Béatrice Nicolaï; Jacco Van de Streek; Nathalie Mahé; René Ceolin; Bernard Do

• Book ID: 102395715
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 341 KB
• Volume: 100
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.22672

✦ Synopsis

Polymorphism is important in the field of solid-state behavior of drug molecules because of the continuous drive for complete control over drug properties. By comparing different structures of a series of L-tyrosine alkyl esters, it became apparent that the ethyl ester possesses dimorphism. Its structure was determined by powder diffraction and verified by density functional theory calculations; it is orthorhombic, P2 1 2 1 2 1 with a = 12.8679(8) Å, b = 14.7345(7) Å, c = 5.8333 (4) Å, V = 1106.01(11) Å, and Z = 4. The density of phase II is in line with other tyrosine alkyl esters and its conformation is similar to that of L-tyrosine methyl ester. The hydrogen bonds exhibit similar geometries for phase I and phase II, but the H-bonds in phase I are stronger. The solid II-solid I transition temperature is heating-rate dependent; it levels off at heating rates below 0.5 K min -1 , leading to a transition temperature of 306 ± 4 K. Application of the Clapeyron equation in combination with calorimetric and X-ray data has led to a topological diagram providing the relative stabilities of the two solid phases as a function of pressure and temperature; phase II is stable under ambient conditions.