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Article Dans Une Revue Journal of Pharmaceutical Sciences Année : 2011

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

Résumé

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) angstrom, b = 14.7345(7) angstrom, c = 5.8333 (4) angstrom, V = 1106.01(11) angstrom, 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.

Domaines

Chimie

Dates et versions

hal-04119164 , version 1 (06-06-2023)

Identifiants

Citer

Ivo B. Rietveld, Maria Barrio, Josep‐lluís Tamarit, Béatrice Nicolaï, Jacco van de Streek, et al.. Dimorphism of the prodrug l‐tyrosine ethyl ester: Pressure–temperature state diagram and crystal structure of phase II. Journal of Pharmaceutical Sciences, 2011, 100 (11), pp.4774-4782. ⟨10.1002/jps.22672⟩. ⟨hal-04119164⟩
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