Detecting and Quantifying Microscale Chemical Reactions in Pharmaceutical Tablets by Stimulated Raman Scattering Microscopy
| Autor: | Ronald L. Smith, Benjamin Figueroa, Christopher T. John, Tai Nguyen, Timothy Rhodes, Yongchao Su, Matthew S. Lamm, Sutthilug Sotthivirat, Wei Xu, Dan Fu |
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| Rok vydání: | 2019 |
| Předmět: |
Chemical imaging
Drug Nonlinear Optical Microscopy Hydrochloride media_common.quotation_subject Chemistry Pharmaceutical Disproportionation 010402 general chemistry 01 natural sciences Chemical reaction Analytical Chemistry Excipients chemistry.chemical_compound Molecule Solubility Least-Squares Analysis Dissolution media_common Pioglitazone Chemistry 010401 analytical chemistry Hydrogen-Ion Concentration 0104 chemical sciences Chemical engineering Stearic Acids Tablets |
| Zdroj: | Analytical chemistry. 91(10) |
| ISSN: | 1520-6882 |
| Popis: | It has been estimated that approximately 50% of all marketed drug molecules are manufactured and administered in the form of salts, often with the goal of improving solubility, dissolution rate, and efficacy of the drug. However, salt disproportionation during processing or storage is a common adverse effect in these formulations. Due to the heterogeneous nature of solid drug formulations, it is essential to characterize the drug substances noninvasively at micrometer resolution to understand the molecular mechanism of salt disproportionation. However, there is a lack of such capability with current characterization methods. In this study, we demonstrate that stimulated Raman scattering (SRS) microscopy can be used to provide sensitive and quantitative chemical imaging of the salt disproportionation reaction of pioglitazone hydrochloride (PIO-HCl) at a very low drug loading (1% w/w). Our findings illuminate a water mediated pathway of drug disproportionation and highlight the importance of noninvasive chemical imaging in a mechanistic study of solid-state chemical reactions. |
| Databáze: | OpenAIRE |
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