Calibration-Free Second Harmonic Generation (SHG) Image Analysis for Quantification of Trace Crystallinity Within Final Dosage Forms of Amorphous Solid Dispersions
| Autor: | Jeremy Hinds, Janny Dinh, Paul D. Schmitt, Casey J Smith, Garth J. Simpson, Michael J. Johnson, Paul A. Stroud |
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| Rok vydání: | 2018 |
| Předmět: |
Materials science
Analytical chemistry 02 engineering and technology 01 natural sciences Benzodiazepines Condensed Matter::Materials Science Crystallinity X-Ray Diffraction Spectroscopy Fourier Transform Infrared Wide dynamic range Instrumentation Spectroscopy Anticholesteremic Agents 010401 analytical chemistry Nonlinear optics Second-harmonic generation 021001 nanoscience & nanotechnology Photon counting 0104 chemical sciences Amorphous solid Second Harmonic Generation Microscopy Calibration Particle Crystallization 0210 nano-technology Algorithms Intensity (heat transfer) Tablets |
| Zdroj: | Applied Spectroscopy. 72:1594-1605 |
| ISSN: | 1943-3530 0003-7028 |
| Popis: | A statistical model enables auto-calibration of second harmonic generation (SHG) images for quantifying trace crystallinity within amorphous solid dispersions (ASDs) over a wide dynamic range of crystallinity. In this paper, we demonstrate particle-counting approaches for quantifying trace crystallinity, combined with analytical expressions correcting for particle overlap bias in higher crystallinity regimes to extend the continuous dynamic range of standard particle-counting algorithms through to the signal averaging regime. The reliability of the values recovered by these expressions was demonstrated with simulated data as well as experimental data obtained for an amorphous solid dispersion formulation containing evacetrapib, an Eli Lilly and Company compound. Since particle counting independently recovers the crystalline volume and the SHG intensity, the average SHG intensity per unit volume can be used as an internal calibrant for quantifying crystallinity at higher volume fractions, for which particle counting is no longer applicable. |
| Databáze: | OpenAIRE |
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