Validation of manufacturing process of Diltiazem HCl tablets by NIR spectrophotometry (NIRS).

The goal of this study was to apply the Process Analytical Technology FDA's initiative in pharmaceutical tablets manufacturing. Near Infrared Spectrophotometry (NIRS) was used as a non-destructive, very fast technique requiring no sample preparation. Direct compression powder blends containing Diltiazem HCl as a model drug were pressed into tablets for the calibration and the validation steps. First, a partial least squares model was built to calibrate the NIR spectrometer. Then, this model was validated and compared with a validated UV spectrophotometry reference method. For this comparison, the Bland and Altman's statistical method was applied. The manufacturing process was validated by producing three batches at three different concentration levels. The NIR analysis of these batches was performed during 3 days. This study shows that NIRS can be used to validate the whole manufacturing process and not only as an analytical method for tablets assay. NIRS is an interesting tool to show possible variations during the manufacturing process which could lead the finished product to fall outside of specifications.