Complementing high-throughput X-ray powder diffraction data with quantum-chemical calculations: Application to piroxicam form III

Kaisa Naelapaa, Jacco van de Streek, Jukka Rantanen, A. D. Bond

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


High-throughput crystallisation and characterisation platforms provide an efficient means to carry out solid-form screening during the pre-formulation phase. To determine the crystal structures of identified new solid phases, however, usually requires independent crystallisation trials to produce single crystals or bulk samples of sufficient quantity to carry out high-quality X-ray diffraction measurements. This process could be made more efficient by a robust procedure for crystal structure determination directly from high-throughput X-ray powder diffraction (XRPD) data. Quantumchemical calculations based on dispersion-corrected density functional theory (DFT-D) have now become feasible for typical small organic molecules used as active pharmaceutical ingredients. We demonstrate how these calculations can be applied to complement high-throughput XRPD data by determining the crystal structure of piroxicam form III. These combined experimental/quantumchemical methods can provide access to reliable structural information in the course of an intensive experimentally based solid-form screening activity or in other circumstances wherein single crystals might never be viable, for example, for polymorphs obtained only during high-energy processing such as spray drying or milling. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:42144219, 2012
TidsskriftJournal of Pharmaceutical Sciences
Udgave nummer11
Sider (fra-til)4214-4219
Antal sider6
StatusUdgivet - 2012