(759c) Principal Component Analysis for Pharmaceutical Process and Product Characterization:Case Study From Immediate and Controlled Release Tablet Manufacturing

As an important data analysis technique for reducing dimensionality of complex process data, Principal Component Analysis (PCA) has been widely used in pharmaceutical PAT applications. The objectives of this work were to utilize PCA for: (1) differentiating physical and chemical characteristics of pharmaceutical solid dosage forms; and (2) establishing link among formulation parameters, manufacturing process variables, and pharmaceutical product quality attributes of controlled release dosage form. Immediate-release and controlled-release theophylline tablets were manufactured and subjected to NIR diffuse reflectance spectroscopy analysis. The raw or preprocessed NIR spectral datasets grouped with either constant tablet hardness, or constant formulation chemistry, or constant core tablet API strength were subjected to PCA. It was determined that the first and second principal components track tablet hardness and chemical composition for immediate release tablets, respectively. For the film-coated controlled release tablets, process trajectory for the film-coating process demonstrated an information-critical coating thickness. The controlled-release tablets were subjected to dissolution testing. A link between coating film thickness and drug dissolution rate was identified via integration of PCA and mass-transfer kinetics analysis of coated tablet dissolution process. Therefore, the possibility of using PCA to separate the physical and chemical information embedded with the NIR spectra of tablets, and to depict link among pharmaceutical formulation parameters, processing variables, and performance characteristics of tablets was demonstrated.