On-line monitoring of residual solvent during the pharmaceutical drying process using non-contact infrared sensor: A process analytical technology (PAT) approach

Abstract A novel on-line solvent drying technique has been described that is capable of simultaneously measuring the solvent end point in vapor phase and maintaining high accuracy with precision. The technique used non-contact infrared sensor for monitoring the solvent vapors during the pharmaceutical solvent drying process. The data presented demonstrated that on-line combined with non-contact sensor method had high degree of precision and accuracy for monitoring the end point of the solvent drying. The analysis of the three stages of drying process suggested that end point process can be precisely determined by the combination of principal component analysis–canonical variate analysis (PCA–CVA) and partial least square–canonical variate analysis (PLS–CVA). The PCA–CVA and PLS–CVA combos provided robust and accurate results with more than 97% classification accuracy between three stages. The Chemometric models also predicted the drying stages of the unknown samples. Agglomerative hierarchical clustering was also applied on the drying data to conform the Chemometric drying results that were very similar. Our findings strongly suggest that the on-line non-contact infrared sensor is a powerful tool. This sensor is capable of analyzing samples in less than 1 min and can determine known and unknown molecules with high accuracy. In addition it has the potential for improving the sensitivity of solvents end points measurement during the pharmaceutical processing.