NIR Spectroscopy Applications in the Development of a Compacted Multiparticulate System for Modified Release

摘要

The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to characterize extrusion-spheronized drug beads, lipid-based placebo beads, and modified release tablets prepared from blends of these beads. The tablet drug load (10.5–19.5 mg) of theophylline (2.25 mg increments) and cimetidine (3 mg increments) could easily be differentiated using univariate analyses. To evaluate other tablet attributes (i.e., compression force, crushing force, content uniformity), multivariate analyses were used. Partial least squares (PLS) models were used for prediction and principal component analysis (PCA) was used for classification. The PLS prediction models (R² > 0.98) for content uniformity of uncoated compacted theophylline and cimetidine beads produced the most robust models. Content uniformity data for tablets with drug content ranging between 10.5 and 19.5 mg showed standard error of calibration (SEC), standard error of cross-validation, and standard error of prediction (SEP) values as 0.31, 0.43, and 0.37 mg, and 0.47, 0.59, and 0.49 mg, for theophylline and cimetidine, respectively, with SEP/SEC ratios less than 1.3. PCA could detect blend segregation during tableting for preparations using different ratios of uncoated cimetidine beads to placebo beads (20:80, 50:50, and 80:20). Using NIR chemical imaging, the 80:20 formulations showed the most pronounced blend segregation during the tableting process. Furthermore, imaging was capable of quantitating the cimetidine bead content among the different blend ratios. Segregation testing (ASTM D6940-04 method) indicated that blends of coated cimetidine beads and placebo beads (50:50 ratio) also tended to segregate.