In situ monitoring of the crystalline state of active pharmaceutical ingredients during high-shear wet granulation using a low-frequency Raman probe
| Autor: | Tatsuo Koide, Toshiro Fukami, Hiroshi Hisada, Kazuya Nomura, Varin Titapiwatanakun |
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| Rok vydání: | 2020 |
| Předmět: |
In situ
Materials science Chemistry Pharmaceutical Drug Compounding Pharmaceutical Science 02 engineering and technology Low frequency Spectrum Analysis Raman 030226 pharmacology & pharmacy Excipients Crystal 03 medical and health sciences Granulation symbols.namesake chemistry.chemical_compound 0302 clinical medicine Cellulose Active ingredient Hydroxypropyl cellulose General Medicine 021001 nanoscience & nanotechnology Microcrystalline cellulose Pharmaceutical Preparations Chemical engineering chemistry symbols Crystallization 0210 nano-technology Raman spectroscopy Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 147:1-9 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2019.12.004 |
| Popis: | Optimization of manufacturing processes based on scientific evidence is important in the quality control of active pharmaceutical ingredients (APIs) and drug products, particularly when crystal forms change during production, which could affect subsequent drug performance. In this study, we verified crystalline states using various crystal faces and excipients during high-shear wet granulation based on non-contact low-frequency (LF) Raman probe monitoring. Four model drugs [indomethacin (IND), acetaminophen (APAP), theophylline (TP), and caffeine (CAF) polymorphs and cocrystals] were mixed with microcrystalline cellulose and hydroxypropyl cellulose with the addition of water over time. The LF Raman probe showed comparatively high sensitivity in monitoring 5–20% APAP and IND in a wet mass. Notably, as observed from the characteristic LF Raman peak shifts, form I TP and CAF and their cocrystals were more susceptible to transformation to the monohydrate form than form II. This method was also shown to be applicable in monitoring a commercial formulation of eight excipients and revealed crystalline transformations after 15 min of mixing. Therefore, probe-type LF Raman spectroscopy can be successfully employed to distinguish and monitor the crystalline state of APIs in real time during high-shear wet granulation, in which there is a risk of crystal transformation. |
| Databáze: | OpenAIRE |
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