Miniaturized X-ray powder diffraction assay (MixRay) for quantitative kinetic analysis of solvent-mediated phase transformations in pharmaceutics
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Publication date
30.11.2016
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01A - Journal article
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Parent work
Journal of Pharmaceutical and Biomedical Analysis
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Volume
131
Issue / Number
Pages / Duration
195-201
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Elsevier
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Abstract
Many pharmaceutical compounds exhibit polymorphism, which may result in solvent-mediated phase transformations. Since the polymorphic form has an essential influence on physicochemical characteristics such as solubility or dissolution rate, it is crucial to know the exact polymorphic composition of a drug throughout pharmaceutical development. This study addressed the need to perform quantitative X-ray analysis of polymorphic mixtures on a 96-well scale (MixRay). A calibration of polymorphic mixtures (anhydrate and hydrate) was performed with three model drugs, caffeine, piroxicam, and testosterone, and linear correlations were obtained for all compounds. The MixRay approach for piroxicam was applied to a solubility and residual solid screening assay (SORESOS) to quantify the amount of hydrate and anhydrate corresponding to kinetic bulk concentrations. Changes in these drug concentrations correlated well with the kinetic changes in the residual solid. The influence of excipients on the solid state and kinetic concentrations of piroxicam was also studied. Excipients strongly affected polymorphic transformation kinetics of piroxicam and concentrations after 24h depended on the excipient used. The new calibration X-ray method combined with bulk concentration analysis provides a valuable tool for both pharmaceutical profiling and early formulation development.
Keywords
Miniaturized assay, Quantitative analysis, Solid state transformation, X-ray diffraction
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ISBN
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0731-7085
1873-264X
1873-264X
Language
English
Created during FHNW affiliation
Yes
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Published
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Peer review of the complete publication
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Citation
Kirchmeyer, W., Wyttenbach, N., Alsenz, J., Kuentz, M., & Grassmann, O. (2016). Miniaturized X-ray powder diffraction assay (MixRay) for quantitative kinetic analysis of solvent-mediated phase transformations in pharmaceutics. Journal of Pharmaceutical and Biomedical Analysis, 131, 195–201. https://doi.org/10.1016/j.jpba.2016.08.028