Applications of NIR in early stage formulation development. Part II. Content uniformity evaluation of low dose...

A near infrared method based on principal component analysis (PCA) was developed for predicting content uniformity of low dose tablets manufactured by a direct compression process. The work was conducted in early stage formulation development. NIR spectra of one hundred and eighty tablets from three feasibility batches were used as the pseudo-calibration set. A correlation was established between PCA scores and a set of reference values obtained by HPLC analysis. The reference values were also used to define a concentration range for the active pharmaceutical ingredient to facilitate content uniformity prediction by PCA. Analyses of unknown samples were conducted by forming a prediction set that included the calibration and unknown samples, followed by PCA. Samples from two development batches were predicted using the PCA model and the results were consistent with the reference HPLC values. Remarkably, the model was able to predict CU for tablets that were prepared using different grades of lactose (anhydrous versus monohydrate). Additionally, during this study, the impact of spectrum pretreatments on PCA is demonstrated. A brief discussion is given to highlight the advantages of PCA over partial least squares (PLS) regression for analysis of samples generated in early stage formulation development.