Quantitative Analysis of Pharmaceutical Bilayer Tablets Using Transmission Raman Spectroscopy

Introduction Transmission Raman Spectroscopy (TRS) has become an increasingly applied technology in the analysis of pharmaceutical tablets for quality control purposes and developing formulation and process understanding. One area that has received only cursory attention to date is that of bilayered tablets that represents an unusually challenging situation. This study aims to provide an understanding of the relationship of the active pharmaceutical ingredient (API) content and the transmission Raman spectral response in bilayered pharmaceutical tablets to facilitate development of quantitative models for the prediction of API content in multilayer tablets. Methods and Results The Raman intensity was considered as a function of the Raman photon generation and decay in a layer of interest (the API layer) and Raman photon decay from a second layer (the non-API layer). To separate and understand the various contributions, a variety of tablet configurations were studied and it was found that (1) with increasing the thickness of the non-API layer, the API Raman signal displayed an exponential decay as a function of the non-API layer thickness as well as the total tablet thickness; (2) when only changing API concentration, the Raman signal linearly responds to the API content; and (3) when increasing the weight/thickness of the API layer and keeping the non-API layer constant, the Raman signal reaches a maximum at a particular thickness and then decays as tablets become thicker. The complex spectral response was effectively modeled according to a modified Schrader, Kubelka-Munk model where both the Raman photon generation factor and photon losses were accounted for. Coupling the results of these studies together yields a comprehensive approach for modeling multi-component bilayer tablets. The addition of a beam enhancer on the bottom surface allowed for a selective overenhancement of the bottom layer, which helps in the analysis of thin layers or coatings.