TY - JOUR

T1 - Complementing high-throughput X-ray powder diffraction data with quantum-chemical calculations

T2 - application to piroxicam form III

AU - Naelapaa, Kaisa

AU - van de Streek, Jacco

AU - Rantanen, Jukka

AU - Bond, Andrew

N1 - Copyright © 2012 Wiley Periodicals, Inc.

PY - 2012

Y1 - 2012

N2 - 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. Quantum-chemical 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/quantum-chemical 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.

AB - 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. Quantum-chemical 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/quantum-chemical 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.

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Molecular Structure

KW - Piroxicam

KW - Powder Diffraction

KW - Quantum Theory

U2 - 10.1002/jps.23287

DO - 10.1002/jps.23287

M3 - Journal article

C2 - 22886472

VL - 101

SP - 4214

EP - 4219

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 11

ER -