Early stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging
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Publication date
12/2018
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01A - Journal article
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European Journal of Pharmaceutics and Biopharmaceutics
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133
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Pages / Duration
122-130
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Elsevier
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Abstract
Early stages of crystallization from amorphous solid dispersion (ASD) are typically not detected by means of standard methods like powder X-ray diffraction (XRPD). The aim of this study is therefore to evaluate if fractal analysis based on energy dispersive X-ray imaging can provide the means to identify early signs of physical instability. ASDs of the poorly water-soluble compound, felodipine (FEL) were prepared by solvent evaporation using different grades of HPMCAS, at 50 wt% drug loading. Samples were stored at accelerated conditions of 40 °C. Scanning electron microscopy equipped with an energy-dispersive X-ray spectroscopy (SEM-EDS) was used for elemental mapping of tablet surfaces. Comparative data were generated with a standard XRPD and with more sensitive methods for detection of early instability, i.e. laser scanning confocal microscopy (LSM) and atomic force microscopy (AFM). The SEM-EDS identified changes of drug-rich domains that were confirmed by LSM and AFM. Early changes in drug clusters were also revealed by a multifractal analysis that indicated a beginning phase separation and drug crystallization. Therefore, the presented fractal cluster analysis based on chemical imaging bears much promise as a new method to detect early signs of physical instability in ASD, which is of great relevance for pharmaceutical development.
Keywords
Solid dispersion, Amorphous drug, Phase separation, Crystallization, Chemical imaging, Multifractal analysis
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0939-6411
1873-3441
1873-3441
Language
English
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Yes
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Published
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Citation
KUENTZ, Martin, Renata ABREU-VILLELA, Monica SCHÖNENBERGER und Isidoro CARABALLO, 2018. Early stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging. European Journal of Pharmaceutics and Biopharmaceutics. Dezember 2018. Bd. 133, S. 122–130. DOI 10.1016/j.ejpb.2018.10.007. Verfügbar unter: http://hdl.handle.net/11654/26982