Multivariate Image and Texture Analysis to Investigate the Erosion Mechanism of Film-coated Tablets: An Industrial Case Study

Introduction The Quality by Design initiative requires the design space of a process to be based on metrics that are robust and reproducible, and not on qualitative ones thatmight be easily biased by human perception. Hence, the use of image analysis is attractive for practical industrial applications where the quality assessment is still typically performed by a panel of trained experts. Methods The use of multivariate image and texture analysis is proposed in this study to quantitatively characterize the elegance of film-coated tablets. Four unsupervised metrics are developed to quantify both the color uniformity of tablet faces/bands and the surface erosion. To develop robust statistics, more than 7,000 tablets coated in nine different pilotscale batches are considered. Latent variable modeling is used to regress the measured elegance against coating operating conditions to investigate the driving forces acting on the system and guide pharmaceutical manufacturing, consistently with the Quality by Design framework. Results The model allows one to successfully investigate the causes leading to tablet erosion. Additionally, it is shown that the model space can be effectively used as a monitoring chart of the overall batch elegance in terms of color uniformity and surface erosion, since the batches are found to rank according to the surface roughness of the manufactured tablets. Conclusions Image analysis has been shown to be an effective process analytical technology for the development of the design space of a film-coating process, where quality assessment on the final product is traditionally based on the judgment of panel of trained experts.