Active content determination of pharmaceutical tablets using near infrared spectroscopy as Process Analytical Technology tool.

The aim of this study was to develop Near infrared (NIR) methods to determine the active content of non-coated pharmaceutical tablets manufactured from a proportional tablet formulation. These NIR methods intend to be used for the monitoring of the active content of tablets during the tableting process. Firstly, methods were developed in transmission and reflection modes to quantify the API content of the lowest dosage strength. Secondly, these methods were fully validated for a concentration range of 70-130% of the target active content using the accuracy profile approach based on β-expectation tolerance intervals. The model using the transmission mode showed a better ability to predict the right active content compared to the reflection one. However, the ability of the reflection mode to quantify the API content in the highest dosage strength was assessed. Furthermore, the NIR method based on the transmission mode was successfully used to monitor at-line the tablet active content during the tableting process, providing better insight of the API content during the process. This improvement of control of the product quality provided by this PAT method is thoroughly compliant with the Quality by Design (QbD) concept. Finally, the transfer of the transmission model from the off-line to an on-line spectrometer was efficiently investigated.