Dispersive Raman Spectroscopy for Quantifying Amorphous Drug Content in Intact Tablets.
| Autor: | Wabuyele BW; Process Analytical Technologies, Merck Manufacturing Division, Merck & Co., Inc., Rahway, New Jersey 07065. Electronic address: busolo.wabuyele@merck.com., Sotthivirat S; Pharmaceutical Sciences & Clinical Supplies, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486., Zhou GX; Process Analytical Technologies, Merck Manufacturing Division, Merck & Co., Inc., Rahway, New Jersey 07065., Ash J; Center for Materials Science and Engineering, Merck Manufacturing Division, Merck & Co., Inc., Rahway, New Jersey 07065., Dhareshwar SS; Pharmaceutical Sciences & Clinical Supplies, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of pharmaceutical sciences [J Pharm Sci] 2017 Feb; Vol. 106 (2), pp. 579-588. Date of Electronic Publication: 2016 Dec 06. |
| DOI: | 10.1016/j.xphs.2016.10.014 |
| Abstrakt: | Process-induced inadvertent phase change of an active pharmaceutical ingredient in a drug product could impact chemical stability, physical stability, shelf life, and bioperformance. In this study, dispersive Raman spectroscopy is presented as an alternative method for the nondestructive, high-throughput, at-line quantification of amorphous conversion. A quantitative Raman method was developed using a multivariate partial least squares (PLS) regression calibration technique with solid-state nuclear magnetic resonance (ssNMR) spectroscopy as the reference method. Compositionally identical calibration tablets containing 20% w/w total MK-A drug in varying weight proportions (0%-50% w/w based on total MK-A) of amorphous and crystalline MK-A were compressed at 10-45 kN force. PLS predictions of amorphous content of tablets using Raman spectroscopy correlated well with ssNMR quantification. The predictive accuracy of this model led to a strong correlation (R 2 = 0.987) with a root mean-squared error of prediction of 1.5% w/w amorphous MK-A in tablets up to 50% w/w amorphous conversion in compressive stress range of 60-320 MPa. Overall, these results suggest that dispersive Raman spectroscopy offers fast, sensitive, and high-throughput (<5 min/tablet) method for quantitating amorphous conversion. (Copyright © 2017. Published by Elsevier Inc.) |
| Databáze: | MEDLINE |
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