title: Dimorphism of the prodrug L-tyrosine ethyl ester: pressure-temperature state diagram and crystal structure of phase II.
abstract: 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.
authors.affiliation: Laboratoire de Chimie Physique (EA4066), Faculté de Pharmacie, Université Paris Descartes, 75006 Paris, France. ivo.rietveld@parisdescartes.fr
authors.forename: Ivo B
authors.initials: IB
authors.lastname: Rietveld
authors.forename: Maria
authors.initials: M
authors.lastname: Barrio
authors.forename: Josep-Lluís
authors.initials: JL
authors.lastname: Tamarit
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nicolaï
authors.forename: Jacco
authors.initials: J
authors.lastname: Van de Streek
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mahé
authors.forename: René
authors.initials: R
authors.lastname: Ceolin
authors.forename: Bernard
authors.initials: B
authors.lastname: Do
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D033362:Powder Diffraction; D011312:Pressure; D011355:Prodrugs / Q000737:chemistry*; D013696:Temperature; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D011355:Prodrugs; D014443:Tyrosine; C051772:ethyl tyrosine ester