Method development and validation for pharmaceutical tablets analysis using transmission Raman spectroscopy

The objective of the study is to demonstrate the development and validation of a transmission Raman spectroscopic method using the ICH-Q2 Guidance as a template. Specifically, Raman spectroscopy was used to determine niacinamide content in tablet cores. A 3-level, 2-factor full factorial design was utilized to generate a partial least-squares model for active pharmaceutical ingredient quantification. Validation of the transmission Raman model was focused on figures of merit from three independent batches manufactured at pilot scale. The resultant model statistics were evaluated along with the linearity, accuracy, precision and robustness assessments. Method specificity was demonstrated by accurate determination of niacinamide in the presence of niacin (an expected related substance). The method was demonstrated as fit for purpose and had the desirable characteristics of very short analysis times (∼2.5s per tablet). The resulting method was used for routine content uniformity analysis of single dosage units in a stability study.

Graphical abstractA partial least-squares model developed from a 3-by-3 full factorial design was used to predict niacinamide content in three different tablet datasets: a test set, a specificity set and a validation set. Factors varied in the design were: active ingredient content, excipient content, relative humidity, compression force and amount of niacin spiked in different tablet groups.Figure optionsDownload full-size imageDownload high-quality image (209 K)Download as PowerPoint slide