A Novel Approach to Evaluate Amorphous-to-Crystalline Transformation of Active Pharmaceutical Ingredients in Solid Dispersion Using Time-Domain NMR
Autor: | Atsushi Kosugi, Shungo Kumada, Yoshinori Onuki, Yoshihiro Hayashi, Kotaro Okada, Daijiro Hirai |
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Rok vydání: | 2019 |
Předmět: |
Active ingredient
Magnetic Resonance Spectroscopy Polyvinylpyrrolidone 010405 organic chemistry Chemistry Spin–lattice relaxation Solid-state General Chemistry General Medicine 010402 general chemistry 01 natural sciences Phase Transition 0104 chemical sciences Amorphous solid Transformation (function) Pharmaceutical Preparations Chemical engineering Drug Discovery medicine Time domain Crystallization Dispersion (chemistry) Powder Diffraction medicine.drug |
Zdroj: | Chemical and Pharmaceutical Bulletin. 67:265-270 |
ISSN: | 1347-5223 0009-2363 |
Popis: | The aim of this study was to demonstrate the usefulness of the time-domain NMR (TD-NMR) method to characterize the crystalline state of active pharmaceutical ingredients (APIs) containing a solid dispersion. In this study, indomethacin (IMC) was used as a model for poorly water-soluble API. Solid dispersions of IMC were prepared with polyvinylpyrrolidone (PVP) at different weight ratios. First, we measured the T1 relaxation behavior of solid dispersions. From the result, the T1 relaxation time (T1) changed according to the API content; the T1 tended to increase with increasing API content because the T1 value of amorphous IMC was longer than that of PVP. Next, we tried to monitor the amorphous-to-crystalline transformation of IMC in the solid dispersion during the thermal stress test. In the case of solid dispersion containing 90% IMC, a clear prolongation of the T1 could be observed during the thermal stress test. From the powder X-ray diffraction patterns, the change in T1 relaxation behavior must be caused by the IMC transformation from amorphous to crystalline. From these findings, we were successful in monitoring the IMC amorphous-to-crystalline transformation by the changes in T1 relaxation behavior. Our findings led us to conclude that TD-NMR is a novel approach for the evaluation of crystalline state of APIs in solid dispersions. |
Databáze: | OpenAIRE |
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