Quantification of drug contents in molded tablets via transmission low-frequency Raman spectroscopy

Abstract

Orally disintegrating tablets (ODTs) are useful for elderly and pediatric patients suffering from difficulty in swallowing conventional tablets. Among various ODT preparing processes, wet tableting involves a process of the low-pressure compression of wet granules followed by drying, which is promising for the industrial production of medicines. Currently, the quality of wet molded tablets is analyzed via conventional high-performance liquid chromatography-based content uniformity tests. However, owing to the low compression pressure required for the wet tableting process, integrating spectroscopic probes with the tableting process can be a potential technique for real-time quality assurance. This study explores the use of transmission low-frequency Raman spectroscopy as a nondestructive and efficient approach for quantifying active pharmaceutical ingredients (APIs) in molded tablets. Acetaminophen and D-mannitol were used as the model API and excipient, respectively. Tablets were prepared by compressing under 150 and 300 N followed by analysis using the partial least squares regression method. The distinct spectral features of acetaminophen and D-mannitol enabled accurate quantification with good linear correlations (R² = 0.98) and low root mean square prediction errors (1.59 for 150 N; 1.22 for 300 N). The method was effective under compressed forces, highlighting it as a real-time, nondestructive tool for quality control in pharmaceutical manufacturing. This approach aligns with continuous manufacturing and quality by design.