Quantitation of Crystalline Material within a Liquid Vehicle using 1H/19F CP/MAS NMR

A method to detect and quantify a small amount crystalline material within a liquid solution of solubilized material is described. 19F CP-MAS ssNMR was investigated as a technique to detect low levels (0.2 mg /g) of crystalline sodium (2R)-7-{3-[2-chloro-4-(2,2,2-trifluoroethoxy)phenoxy]propoxy}-2-methyl-3,4-dihydro-2H-chromane-2-carboxylate (I) within a solid mixture (with microcrystalline cellulose) and a slurry with a liquid vehicle (capric and caprylic acid triglycerides). The results demonstrate that the area of the 19F CP/MAS signal obtained in 25 minat 25°C is linearly dependent (R2 = 0.997) on the mass of I within the ssNMR rotor. Slopes of CP-MAS peak area versus mass of I in the rotor were nearly identical for the solid mixture and slurry suspension. Signal-to-noise ratio for the low potency slurry suggest detection and quantitation of 0.1 mgof crystalline I in the rotor, corresponding to 2 mg /g of crystalline material within the slurry suspension. ©2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:264-267, 2007