Determination of the composition of delavirdine mesylate polymorph and pseudopolymorph mixtures using 13C CP/MAS NMR

The application of solid-state nuclear magnetic resonance for the quantitation of relative amounts of delavirdine mesylate (DLV-M) polymorph and/or pseudopolymorph in their binary mixtures is presented.

13C CP (cross-polarization)/MAS (magic angle spinning) NMR techniques were employed for quantitation.

13C CP/MAS NMR spectra of three DLV-M solid forms (VIII, XI, and XII) revealed distinct differences in chemical shifts and peak splitting characteristics. Resonances of isopropyl methyl carbons of DLV-M were diagnostic of each form; resonance intensities were utilized to determine the composition of two series of DLV-M solid form mixtures (VIII and XI; XII and XI) over a dynamic concentration range (1-50%). The empirical detection limit of form VIII, or XII, in a dominant form XI environment was about 2-3% (w/w). Quantitations were obtained using appropriate analytical procedures, which took into account the differences of TCH and T1pH between the two forms. Quantitative results obtained using either the peak area or peak height were examined, and, in general, were satisfactory.

The methodology and analytical procedure developed in this study are generally applicable to quantitative analysis using 13C CP/MAS NMR for pharmaceutical solids, including bulk drug substances, and dosage forms. Reliable measurement of NMR relaxation times (T1pH) and CP rate constants (TCH) of individual forms is a critical component in this application.