Real-time determination of critical quality attributes using near-infrared spectroscopy: a contribution for Process Analytical Technology (PAT).

Abstract Process Analytical Technology (PAT) is playing a central role in current regulations on pharmaceutical production processes. Proper understanding of all operations and variables connecting the raw materials to end products is one of the keys to ensuring quality of the products and continuous improvement in their production. Near infrared spectroscopy (NIRS) has been successfully used to develop faster and non-invasive quantitative methods for real-time predicting critical quality attributes (CQA) of pharmaceutical granulates (API content, pH, moisture, flowability, angle of repose and particle size). NIR spectra have been acquired from the bin blender after granulation process in a non-classified area without the need of sample withdrawal. The methodology used for data acquisition, calibration modelling and method application in this context is relatively inexpensive and can be easily implemented by most pharmaceutical laboratories. For this purpose, Partial Least-Squares (PLS) algorithm was used to calculate multivariate calibration models, that provided acceptable Root Mean Square Error of Predictions (RMSEP) values (RMSEP API =1.0 mg/g; RMSEP pH =0.1; RMSEP Moisture =0.1%; RMSEP Flowability =0.6 g/s; RMSEP Angleofrepose =1.7° and RMSEP Particle size =2.5%) that allowed the application for routine analyses of production batches. The proposed method affords quality assessment of end products and the determination of important parameters with a view to understanding production processes used by the pharmaceutical industry. As shown here, the NIRS technique is a highly suitable tool for Process Analytical Technologies.