Pharmaceutical Applications of Relaxation Filter-Selective Signal Excitation Methods for 19F Solid-State Nuclear Magnetic Resonance: Case Study With Atorvastatin in Dosage Formulation

We recently developed several new relaxation filter-selective signal excitation (RFS) methods for C-13 solid-state nuclear magnetic resonance (NMR) that allow C-13 signal extraction of the target components from pharmaceuticals. These methods were successful in not only qualification but also quantitation over the wide range of 5% to 100%. Here, we aimed to improve the sensitivity of these methods and initially applied them to F-19 solid-state NMR, on the basis that the fluorine atom is one of the most sensitive NMR-active nuclei. For testing, we selected atorvastatin calcium (ATC), an antilipid BCS class II drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase and is marketed in crystalline and amorphous forms. Tablets were obtained from 2 generic drug suppliers, and the ATC content occurred mainly as an amorphous form. Using the RFS method with F-19 solid-state NMR, we succeeded in qualifying trace amounts (less than 0.5% w/w level) of crystalline phase (Form I) of ATC in the tablets. RFS methods with F-19 solid-state NMR are practical and time efficient and can contribute not only to the study of pharmaceutical drugs, including those with small amounts of a highly potent active ingredient within a formulated product, but also to the study of fluoropolymers in material sciences. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.