DETERMINATION OF THE COMPOSITION OF DELAVIRDINE MESYLATE POLYMORPH AND PSEUDOPOLYMORPH MIXTURES USING C-13 CP MAS NMR/

Purpose. 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 . Methods. C-13 CP (cross-polarization)/MAS (magic angle spinning) NMR techniques were employed for quantitation. Results. C-13 CP/MAS NMR s pectra of three DLV-M solid forms (VIII, XI, and XII) revealed distinc t differences in chemical shifts and peak splitting characteristics. R esonances of isopropyl methyl carbons of DLV-M were diagnostic of each form; resonance intensities were utilized to determine the compositio n 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 l imit 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 T-CH and T-1pH between the two forms. Quantitative results obtained using either the peak area or peak height were examined, and, in general, were satisfac tory. Conclusions. The methodology and analytical procedure developed in this study are generally applicable to quantitative analysis using C-13 CP/MAS NMR for pharmaceutical solids, including bulk drug substan ces, and dosage forms. Reliable measurement of NMR relaxation times (T -1pH) and CP rate constants (T-CH) Of individual forms is a critical c omponent in this application.