Background: The stability of the finished medicinal product has a significant impact on the effectiveness of the medicinal product as well as the safety of the patient. With this in mind, stability testing is now a legal requirement for medicinal products throughout the drug development process. In the present study, the stability of effervescent tablets was assessed using a non-invasive X-ray microtomography technique.
Methods: Two types of effervescent tablets of one commercial product containing vitamin C which is available at the Polish market were analyzed, i.e. unexpired (expiration date: 04.2023) and expired (expiration date: 02.2020). X-ray microtomography (GE Sensing & Inspection Technologies GmbH, Wunstorf, Germany) was used to register the scans of analyzed tablets. The tablets were scanned at a voltage of 180 kV. An object analyzed by this method absorbs X-rays in proportion to its density. In the microtomographic image, the density is reflected by the gray level, i.e. “bright” pixels represent areas of high density, while “dark” pixels represent areas of low density. A phantom with known density areas (Micro-CT HA Phantom D32) was scanned together with effervescent tablets to establish the grayscale level of the reference density.
Results: We analyzed 70 random regions of interest (ROIs) from the 20 microtomographic slices of each type of the effervescent tablets. The average brightness of the pixels was measured with ImageJ software. A curve of dependence between brightness and density of known area from the phantom was drawn. A significant difference was observed in the density of the inner structure between the two types of analyzed effervescent tablets with vitamin C (p<0.001). The higher mean density was observed in the case of unexpired tablets (1.250 g/cm3) compared to expired tablets (1.242 g/cm3). Thus, unexpired effervescent tablets containing vitamin C showed better homogeneity than expired ones.
Conclusions: The applied method of three-dimensional µCT imaging allowed rapid detection of differences in the microstructure of expired and unexpired tablets. On the basis of quantitative data, significant differences in the tablet density of the studied drug forms were demonstrated.
