Cost-Efficient and Fast At-Line Assessment of Content and Uniformity in Low-Dose Dimdazenil Capsules Using...

Background/Objectives: Transmission Raman spectroscopy (TRS) is widely used for non-destructive quantification of solid dosage forms, yet most applications involve high-dose formulations (>5% w/w active pharmaceutical ingredient (API)). This study addresses the underexplored area of low-dose drug analysis by developing a TRS method for dimdazenil capsules containing only ~1.5% w/w API-a concentration rarely reported in the current TRS literature. Methods: A partial least squares (PLS) model was built using TRS spectra of dimdazenil capsules, with sample variability introduced via a design of experiments (DoE) approach. Model performance was validated against reference high-performance liquid chromatography (HPLC) data from independent samples and three commercial batches, incorporating specificity checks and greenness assessment via AGREEprep. Results: The TRS method achieved reliable variation assessment with acceptable accuracy, showing relative errors below 5.0% across all validation sets despite a minor systematic bias of ~-2.87%. Analysis required no sample preparation and took less than 150 s per capsule. Specificity was ensured by the unique 1628 cm^-1 band of dimdazenil, with no interference from excipients confirmed by spectral examination and multivariate statistical methods. The method scored 0.86 on AGREEprep, highlighting its environmental superiority over HPLC. Conclusions: This work demonstrates that TRS can be reliably extended to low-dose solid dosage forms (~1.5% w/w), a concentration range rarely addressed in the existing TRS literature. This significantly broadens its applicability in pharmaceutical quality control and supports its potential integration into continuous manufacturing for challenging low-concentration products.