Quantitative Component Analysis of Solid Mixtures by Analyzing Time Domain 1H and 19F T1 Saturation Recovery Curves (qSRC)

Prevalent polymorphism and complicated phase behavior of active pharmaceutical ingredients (APIs) often result in remarkable differences in the respective biochemical and physical API properties. Consequently, API form characterization and quantification play a central role in the pharmaceutical industry from early drug development to manufacturing. Here we present a novel and proficient quantification protocol for solid mixtures (qSRC) based on the measurement and mathematical fitting of T1 nuclear magnetic resonance (NMR) saturation recovery curves collected on a bench top time-domain NMR instrument. The saturation recovery curves of the relevant pure components are used as fingerprints. Employing a bench top NMR instrument possesses clear benefits. These instruments exhibit a small footprint, do not present any special requirements on lab space, and required sample handling is simple and fast. The qSRC analysis can easily be conducted in a conventional laboratory setting as well as in an industrial production environment, making it a versatile tool with the potential for widespread application. The accuracy and efficiency of the qSRC method is illustrated using 1H and 19F T1 data of selected pharmaceutical model compounds, as well as utilizing 1H T1 data of an actual binary API anhydrous polymorph system of a Merck & Co., Inc. compound formerly developed as a hepatitis C virus drug.