Electron microscopy/energy dispersive X-ray spectroscopy of drug distribution in solid dispersions and interpretation by multifractal geometry
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Publication date
2018
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Type
01A - Journal article
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Parent work
Journal of Pharmaceutical and Biomedical Analysis
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Volume
150
Issue / Number
Pages / Duration
241-247
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Publisher / Publishing institution
Elsevier
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Abstract
Much contemporary research of poorly water-soluble drugs focuses on amorphous solid dispersions (SDs) for oral drug delivery. Recently, a multifractal formalism has been introduced to describe the distribution of an inorganic carrier in SDs. The present work attempts to directly image model drugs by means of scanning electron microscopy and energy dispersive X-ray spectroscopy. The compounds amlodipine, felodipine, glyburide, and indomethacine, which include halogens to enable sufficient scattering in energy dispersive X-ray spectroscopy, were employed to prepare SDs with hydroxypropyl methylcellulose acetate succinate (HPMCAS) by using a microwave method. Following chemical imaging, it was demonstrated that drug distribution was best described by multifractals, which was clearly superior to a monofractal assumption. The obtained fractal dimensions were influenced by drug loading and it was possible to detect microstructural changes upon addition of the plasticizer urea. Accordingly, the multifractal approach bears much potential to better explore the analytical results of chemical formulation imaging. Insights can be gained from the microstructural organization of SDs, which is interesting to further study formulation and process factors as well as physical stability.
Keywords
Solid dispersion, Microstructure, Fractal dimension, Scanning electron microscopy, Multifractal
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ISBN
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0731-7085
1873-264X
1873-264X
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
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Peer review of the complete publication
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Citation
Abreu-Villela, R., Adler, C., Caraballo, I., & Kuentz, M. (2018). Electron microscopy/energy dispersive X-ray spectroscopy of drug distribution in solid dispersions and interpretation by multifractal geometry. Journal of Pharmaceutical and Biomedical Analysis, 150, 241–247. https://doi.org/10.1016/j.jpba.2017.12.020