Time-domain NMR analysis for the determination of water content in pharmaceutical ingredients and wet granules

Abstract

The application of time-domain NMR (TD-NMR) analysis to quantify water content in pharmaceutical ingredients is demonstrated. The initial phase of the study employed a range of disintegrants with defined amounts of added water (0–30% of the total weight) as samples; the disintegrants included croscarmellose sodium, corn starch, low-substituted hydroxypropyl cellulose, and crospovidone. After acquisition of the T2 relaxation curves of the samples by TD-NMR measurements, these curves were analyzed by partial least squares (PLS) regression. According to the analysis, accurate and reliable PLS models were created that enabled accurate assessment of water content in the samples. A powder blend consisting of acetaminophen (paracetamol) and tablet excipients was also examined. Both a physical mixture of the powder blend and a wet granule prepared with a high-speed granulator were tested as samples in this study. Precise determination of water content in the powder blend was achieved by using the TD-NMR method. The accuracy of water content determination was equivalent to or better than that of the conventional loss on drying method. TD-NMR analysis samples were measured nondestructively and rapidly with low cost; thus, it could be a powerful quantitative method for determining water content in pharmaceuticals.