The dissolution method is still widely used to determine curing end-points to ensure long-term stability of film coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat)-based coated tablets. X-ray micro-computed tomography (XμCT), Near Infrared (NIR), and Raman spectroscopies as well as X-ray microdiffraction were employed as non-destructive techniques to perform direct measurements on tablets. All techniques indicated that after a dynamic curing period of 4h, reproducible drug release can be achieved and no changes in the microstructure of the coating were any longer detected. XμCT analysis highlighted the reduced internal porosity, while both NIR and Raman measurements showed that spectral information remained unaltered after further curing. X-ray microdiffraction revealed densification of the coating layer with a decrease in the overall coating thickness of about 10 μm as a result of curing. In addition, coating heterogeneity attributed to cetyl alcohol was observed from microscopic images and Raman analysis. This observation was confirmed by X-ray microdiffraction that showed that crystalline cetyl alcohol melted and spread over the coating surface with curing. Prior to curing, X-ray microdiffraction also revealed the existence of two coating zones differing in crystalline cetyl alcohol and sodium lauryl sulfate concentrations which could be explained by migration of these constituents within the coating layer. Therefore, the use of non-destructive techniques allowed new insights into tablet coating structures and provided precise determination of the curing end-point compared to traditional dissolution testing. This thorough study may open up new possibilities for process and formulation control.
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