Characterizing process effects on pharmaceutical solid forms using near-infrared spectroscopy and infrared imaging.

Near-infrared spectroscopy (NIRS) has become a widely used analytical technique in the pharmaceutical industry, serving for example to determine the active substance or water content of tablets. Its great advantage lies in the minimal sample preparation required and speed of measurement. In a study designed to detect the effects of process on tablet dissolution, we describe the application of NIRS to the detection and identification of changes in uncoated and coated tablets in response to pilot-scale changes in process parameters during melt granulation, compression, and coating. Beginning with a qualitative comparison between pharmaceutical batches, we show that NIRS and principal component analysis can separate batches produced with different melt granulation parameters and differentiate between cores compressed with different compaction forces. Complementary infrared imaging can also explain the difference in dissolution properties between samples produced with different melt granulation parameters. NIRS is sensitive to changes in coating formulation, the quality of a coating excipient (hydroxypropyl methylcellulose), and coating time. In a concluding quantitative analysis, we demonstrate the feasibility of NIRS in a manufacturing context for predicting coating time and detecting production cores failing to meet dissolution test specifications.