Kinetic Modeling of Accelerated Stability Testing Enabled by Second Harmonic Generation Microscopy
| Autor: | Sreya Sarkar, Andrew D. Vogt, Zhengtian Song, Garth J. Simpson, Casey J Smith, Ellen J. Gualtieri, Gerald D. Danzer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Chemistry 010401 analytical chemistry Analytical chemistry Second-harmonic generation 02 engineering and technology Polymer Second Harmonic Generation Microscopy 021001 nanoscience & nanotechnology 01 natural sciences 0104 chemical sciences Analytical Chemistry Amorphous solid law.invention Matrix (chemical analysis) law Microscopy Solubility Crystallization 0210 nano-technology |
| Zdroj: | Analytical Chemistry. 90:4406-4413 |
| ISSN: | 1520-6882 0003-2700 |
| DOI: | 10.1021/acs.analchem.7b04260 |
| Popis: | The low limits of detection afforded by second harmonic generation (SHG) microscopy coupled with image analysis algorithms enabled quantitative modeling of the temperature-dependent crystallization of active pharmaceutical ingredients (APIs) within amorphous solid dispersions (ASDs). ASDs, in which an API is maintained in an amorphous state within a polymer matrix, are finding increasing use to address solubility limitations of small-molecule APIs. Extensive stability testing is typically performed for ASD characterization, the time frame for which is often dictated by the earliest detectable onset of crystal formation. Here a study of accelerated stability testing on ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, has been conducted. Under the condition for accelerated stability testing at 50 °C/75%RH and 40 °C/75%RH, ritonavir crystallization kinetics from amorphous solid dispersions were monitored by SHG microscopy. SHG microscopy coupled by image analysis yielded limits of detection for ritonavir crystals as low as 10 ppm, which is about 2 orders of magnitude lower than other methods currently available for crystallinity detection in ASDs. The four decade dynamic range of SHG microscopy enabled quantitative modeling with an established (JMAK) kinetic model. From the SHG images, nucleation and crystal growth rates were independently determined. |
| Databáze: | OpenAIRE |
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