title: [Crystallography of drug polymorphism: emergence of new resolution methods and prediction of crystalline structures].
abstract: For the pharmaceutical and agrochemical industries, reducing development time is currently a primary objective to accelerate the marketing of new products. In-depth solid-state characterization is an essential element in achieving this performance. For this purpose, it is now recognized that, in a department of solid-state physical characterization, theoretical approaches have to be integrated with experimental tools. Benefiting from the constant improvement in computer hardware and software in terms of computing powers and algorithm development, these approaches appear to be a complementary method that can help explain and rationalize experimental data. In recent years, with the help of both molecular modeling tools and crystallographic databases, original methods have been developed and successfully applied to systems of variable complexity. The X-ray diffraction crystal structure determination makes it possible to calibrate the force field and to adapt it more precisely to the compound studied, thereby reducing one of the sources of uncertainty. Although crystal structures are preferentially determined from single crystal data, it has been recently shown that powder diffraction data can also be used when single crystals are missing. Therefore, the different benefits of such an approach are the following: ab initio predictive study of crystalline polymorphism, molecular packing analysis and detection of cleavage planes, prediction of morphology in vacuum. In conjunction with crystallite preferred orientation observed in powder patterns, grinding effects on the crystal habit and solvent effects in modifying growth can be clearly understood. Selected industrial cases exemplify the operational application of this methodology.
authors.affiliation: Aventis Pharma, Sciences pharmaceutiques, Centre de recherche de Paris, 13, quai Jules Guesde, F94400 Vitry sur Seine, France. marc-antoine.perrin@aventis.com
authors.forename: M A
authors.initials: MA
authors.lastname: Perrin
mesh_terms: D003460:Crystallization; D000077143:Docetaxel; D007212:Indolizines / Q000737:chemistry; D008968:Molecular Conformation; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D043823:Taxoids
chemical_list: C434923:2-chloro-3-pyridine-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide; D007212:Indolizines; D004364:Pharmaceutical Preparations; D011725:Pyridines; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel
vernacular_title: Cristallographie du polymorphisme des médicaments: émergence de nouvelles méthodes de résolution et de prédiction de structures cristallines.