Evaluation of distributional homogeneity of pharmaceutical formulation using laser direct infrared imaging

Abstract

The distributional homogeneity of chemicals is a key parameter of solid pharmaceutical formulations. Indeed, it may affect the efficacy of the drug and consequently its safety.Chemical imaging offers a unique insight enabling the visualisation of the different constituents of a pharmaceutical tablet. It allows identifying ingredients poorly distributed offering the possibility to optimize the process parameters or to adapt characteristics of incoming raw materials to increase the final product quality.Among the available chemical imaging tools, Raman imaging is one of the most widely used since it offers a high spatial resolution with well-resolved peaks resulting in a high spectral specificity. However, Raman imaging suffers from sample autofluorescence and long acquisition times. Recently commercialised, laser direct infrared reflectance imaging (LDIR) is a quantum cascade laser (QCL) based imaging technique that offers the opportunity to rapidly analyse samples.In this study, a typical pharmaceutical formulation blend composed of two active pharmaceutical ingredients and three excipients was aliquoted at different mixing timepoints. The collected aliquots were tableted and analysed using both Raman and LDIR imaging. The distributional homogeneity indexes of one active ingredient image were then computed and compared. The results show that both techniques achieved similar conclusions. However, the analysis times were drastically different. While Raman imaging required a total analysis time of 4 h per tablet to obtain the distribution map of acetylsalicylic acid with a step size of 100 µm, it only took 7.5 min to achieve the same result with LDIR.The results obtained in the present study show that LDIR is a promising technique for the analysis of pharmaceutical formulations and that it could be a valuable tool when developing new pharmaceutical formulations.