title: Method development and validation for pharmaceutical tablets analysis using transmission Raman spectroscopy.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Duquesne Center for Pharmaceutical Technology, Duquesne University, 600 Forbes Avenue, Pittsburgh PA 15282, United States.
authors.forename: Benoît
authors.initials: B
authors.lastname: Igne
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States; Duquesne Center for Pharmaceutical Technology, Duquesne University, 600 Forbes Avenue, Pittsburgh PA 15282, United States.
authors.forename: James K
authors.initials: JK
authors.lastname: Drennen
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States; Duquesne Center for Pharmaceutical Technology, Duquesne University, 600 Forbes Avenue, Pittsburgh PA 15282, United States. Electronic address: andersonca@duq.edu.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods; D013607:Tablets / Q000032:analysis* / Q000737:chemistry*
chemical_list: D013607:Tablets
keywords: ICH-Q2; Stability-indicating assay; Transmission Raman spectroscopy; Validation