Quantitative Measures of Crystalline Fenofibrate in Amorphous Solid Dispersion Formulations by X-Ray Microscopy

Neilly, Joseph; Yin, Leilei; Leonard, Sarah E.; Kenis, Paul J. A.; Danzer, Gerald D.; Pawate, Ashtamurthy S.

doi:10.1016/j.xphs.2020.07.006

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…The grey scale in the X-ray μCT images is related to the density and the average atomic number of components within the tablet: high density areas are brighter compared to low density areas (e.g. voids) ( Neilly et al, 2020 ). Representative X-ray μCT images show radial and axial cross sections of the tablet midsection for ASD tablets ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Schönfeld

Westedt

Wagner

2021

International Journal of Pharmaceutics: X

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The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

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Section: Resultsmentioning

confidence: 99%

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Schönfeld

Westedt

Wagner

2021

International Journal of Pharmaceutics: X

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“…Crystals in hot melt extruded ASDs have been regularly identified to be smaller than 1 μm ,,, and as small as 5–10 nm . Transmission electron microscopy (TEM) is highly sensitive but low throughput to identify crystals in amorphous systems through electron diffraction. , Scanning electron microscopy (SEM) can be used to detect trace crystallinity based on their distinctive shape but is only useful for detecting surface crystals. , Second harmonic generation is highly sensitive to noncentrosymmetric systems, enabling quantification of trace crystallinity in the parts per billion range. − X-ray micro computed tomography (microCT) is useful to identify low levels of crystallinity (<1%), but resolution is limited to crystals ∼10 μm or greater …”

Section: Crystallinity Detection Methods and In Vitro Performance Tes...mentioning

confidence: 99%

Crystallinity: A Complex Critical Quality Attribute of Amorphous Solid Dispersions

Moseson,

Taylor

2023

Mol. Pharmaceutics

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“…It is uncommon outside of an R&D setting but may be accessible in some development or commercialization QC functions. Evermore sensitive analytical techniques such as SEM, TEM, Secondorder nonlinear optical imaging of chiral crystals (SONNIC) or second-harmonic generation (SHG) microscopy, [31][32][33] μCT 34 and Kinetic Solubility 35 continue to evolve however these newer, noncommercially available and/or niche techniques are constantly evaluated and as they mature may be incorporated into the analytical toolbox.…”

Section: The Analytical 'Toolbox' To Characterize Amorphous Solid Dis...mentioning

confidence: 99%

Industry White Paper: Contemporary Opportunities and Challenges in Characterizing Crystallinity in Amorphous Solid Dispersions

Chasse

Conway

Danzer

et al. 2022

Journal of Pharmaceutical Sciences

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Quantitative Measures of Crystalline Fenofibrate in Amorphous Solid Dispersion Formulations by X-Ray Microscopy

Cited by 10 publications

References 22 publications

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Crystallinity: A Complex Critical Quality Attribute of Amorphous Solid Dispersions

Industry White Paper: Contemporary Opportunities and Challenges in Characterizing Crystallinity in Amorphous Solid Dispersions

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