Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 104, Issue 8, Pages 2550-2558Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.24524
Keywords
crystallinity; amorphous; Raman spectroscopy; solid state NMR; partial least squares
Ask authors/readers for more resources
Warfarin sodium (WS) exists in multiple solid-state forms. The solid-state forms differ in physicochemical properties, and crystalline changes in the drug formulation may influence on the drug product quality and/or clinical performance. It is, therefore, critically important to have a good and reliable analytical method to monitor and quantitate this transformation during stability studies. The aim of the present research was to investigate Raman spectroscopy and solid-state nuclear magnetic resonance (C-13 ssNMR) methods in conjunction with chemometry to quantitate the amorphous and crystalline WS fractions in the drug products. Compositionally identical formulations of amorphous and crystalline WS were prepared, and mixed in various proportions to make 0%-100% amorphous/crystalline sample matrices. Raman and C-13 ssNMR spectra were collected and subjected to partial-least-squares and principle component regressions after mathematical treatment of the data. The model performance parameters such as root-mean-square error of prediction, standard error of prediction, and bias were low for Raman models in comparison to C-13 ssNMR models. Models predicted values of the independent sample matrices match closely with the actual values at high level of crystalline WS. Thus, the developed methods provide means to control and quantitate the WS forms fraction in the drug product. Published 2015. This article is a U.S. Government work and is in the public domain in the USA 104:2550-2558, 2015
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available