Authors:S. Petit, F. Mallet, M. Petit, and G. Coquerel
A combined analysis of structural data and experimental results (DSC, temperature-resolved XRPD and hot stage optical microscopy)
revealed that the dehydration mechanism of cortisone acetate monohydrate (CTA·H2O) involves a collective and anisotropic departure of water molecules followed by a cooperative structural reorganization
toward the anhydrous polymorph CTA (form 2). In spite of the lack of crystal structure data, it can be postulated from experimental
data that thermal decomposition of the dihydrated form (CTA·2H2O) and of the tetrahydrofuran solvate (CTA·THF) toward another polymorph (CTA (form 3)) also proceeds according to a cooperative
mechanism, thus giving rise to probable structural filiations between these crystalline forms of CTA. The crystal structure
determination of two original solvates (CTA·DMF and CTA·DMSO) indicates that these phases are isomorphous to the previously
reported acetone solvate. However, their desolvation behaviour does not involve a cooperative mechanism, as could be expected
from structural data only. Instead, the decomposition mechanism of CTA·DMF and CTA·DMSO starts with the formation of a solvent-proof
superficial layer, followed by the partial dissolution of the enclosed inner part of crystals.
Hot stage optical microscopy observations and DSC measurements showed that dissolved materials (resulting from a peritectic
decomposition) is suddenly evacuated through macroscopic cracks about 30°C above the ebullition point of each solvent. From
this unusual behaviour, the necessity to investigate rigorously the various aspects (thermodynamics, kinetics, crystal structures
and physical factors) of solvate decompositions is highlighted, including factors related to the particular preparation route
of each sample.
Authors:F. Mallet, S. Petit, S. Lafont, P. Billot, D. Lemarchand, and G. Coquerel
Solid-solid transformations between solvates of pharmaceutical compounds are investigated under various conditions. In the
case of Roxithromycin, it is shown that starting from single crystals of the acetonitrile solvate, a transformation towards
the monohydrate occurs according to a cooperative mechanism. This smooth exchange of solvent probably involves a transport
of matter within channels, and the comparison of crystal structures is consistent with the persistence of the main features
of the 3D lattice. By contrast, starting from the DMSO solvate of Dexamethasone acetate, the transformation towards the sesquihydrated
form, induced by the immersion of the DMSO solvate in water, is fully destructive and reconstructive. This occurs far-from-equilibrium
and is therefore controlled by kinetic factors. The existence of an intermediate liquid phase within the particle is postulated
to account for the appearance of whisker-like crystals growing first on high-energy sites of the former particle. An extended
analysis of these transformations between solvates shows that they could be classified according to rules previously proposed
in the case of desolvation mechanisms.
Authors:A. Grandeury, L. Renou, F. Dufour, S. Petit, G. Gouhier, and G. Coquerel
The crystallization behaviour and the physical characterization of supramolecular complexes formed between permethylated-α-cyclodextrin
(TMα-CD) and the enantiomers of phenylethanol (PE) are investigated. According to crystal structure analyses, complexes containing
the pure guest enantiomers are almost isomorphous, indicating that the host presents a poor ability to distinguish PE enantiomers
at a molecular level. Nevertheless, crystallizations from racemic PE in water induce an efficient chiral discrimination and
allow the enantio-separation of the guests despite the existence of a solid solution revealed by XRPD and coupled TG-DSC analyses.
The enantiodifferentiation is explained by solubility differences between the two diastereomeric complexes in the studied
temperature range. Moreover, it is shown that the diastereomeric complex TMα-CD/(S)-PE crystallizes in two distinct phases: a monohydrate and an anhydrous form, with a transition temperature close to 37C.
The insertion of a water molecule in the crystals grown below 37C does not involve any other change of the crystal packing
nor of the molecular conformation, but leads to different crystal growth mechanisms inducing different morphologies and distinct
Authors:P. Povinec, M. Pham, J. Sanchez-Cabeza, G. Barci-Funel, R. Bojanowski, T. Boshkova, W. Burnett, F. Carvalho, B. Chapeyron, I. Cunha, H. Dahlgaard, N. Galabov, L. Fifield, J. Gastaud, J. Geering, I. Gomez, N. Green, T. Hamilton, F. Ibanez, M. Ibn Majah, M. John, G. Kanisch, T. Kenna, M. Kloster, M. Korun, L. Liong Wee Kwong, J. La Rosa, S. Lee, I. Levy-Palomo, M. Malatova, Y. Maruo, P. Mitchell, I. Murciano, R. Nelson, A. Nouredine, J. Oh, B. Oregioni, G. Le Petit, H. Pettersson, A. Reineking, P. Smedley, A. Suckow, T. van der Struijs, P. Voors, K. Yoshimizu, and E. Wyse
A reference material designed for the determination of anthropogenic and natural radionuclides in sediment, IAEA-384 (Fangataufa
Lagoon sediment), is described and the results of certification are presented. The material has been certified for 8 radionuclides
(40K, 60Co, 155Eu, 230Th, 238U, 238Pu, 239+240Pu and 241Am). Information values are given for 12 radionuclides (90Sr, 137Cs, 210Pb (210Po), 226Ra, 228Ra, 232Th, 234U, 235U, 239Pu, 240Pu and 241Pu). Less reported radionuclides include 228Th, 236U, 239Np and 242Pu. The reference material may be used for quality management of radioanalytical laboratories engaged in the analysis of radionuclides
in the environment, as well as for the development and validation of analytical methods and for training purposes. The material
is available from IAEA in 100 g units.