Nathalie Mahé

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

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.

Uniaxial negative thermal expansion in crystals of tienoxolol

The thermal expansion of tienoxolol has been investigated by X-ray powder diffraction up to its melting temperature. The data indicate that the expansion is anisotropic and even negative in one direction of the unit cell. The supramolecular structure formed by hydrogen-bonds reflects that of a trellis, which explains the observed behavior of tienoxolol crystals.

One-pot template extraction and alumination of BEC-type zeolite

The present work reports on the one-pot template extraction and isomorphous substitution of aluminum for germanium in a BEC-type framework. The obtained data show that a partial replacement of Ge with Al in the zeolite framework is possible by post-synthesis wet chemistry methods. Complementary techniques, such as NMR, XRD, TG/DTA, SEM and X-ray fluorescence analyses were employed in order to fully characterize the post-synthesis modified BEC-type samples. Further development of this approach is expected to stabilize Ge-rich zeolite frameworks.

Crystal structure and solid-state studies of aged samples of tienoxolol, an API designed against hypertension

Aging of drug molecules is generally studied following regulatory procedures, i.e. under forced conditions and for relatively limited storage time; therefore naturally aged samples are rare and provide scientific reference data beyond regulatory considerations. Tienoxolol was studied after 25 years of storage in the dark under ambient conditions. About 86% of the samples still consisted of tienoxolol and the main impurity (13%) was caused by the hydrolysis of the ester moiety. Protection from humidity is therefore important. Other sensitive groups containing nitrogen and sulfur appear to be quite stable with less than 0.8% conversion over 25 years. In addition, the crystal structure has been solved. Tienoxolol orange needles were found to crystallize in the orthorhombic non-centrosymmetric space group Iba2, indicating that the crystal is a racemic compound. The unit cell parameters at room temperature are a=10.069(5)Å, b=45.831(10)Å, and c=9.822(5)Å and the unit cell volume is 4533(3)Å(3) with Z=8.