Time-Lapse Macro Imaging with Dissolution Tests for Exploring the Interrelationship Between Disintegration and Dissolution Behaviors of Solid Dosages.

ABSTRACT

OBJECTIVE: This study aims to establish a Flow-through Visualization Dissolution System (FVDS) that combines time-lapse macro-imaging and a flow-through cell to simultaneously elucidate dissolution and disintegration profiles. METHODS: Three cefaclor extended-release tablets (CEC-1, CEC-2, CEC-3) from different manufacturers were subjected to dissolution tests using both the US Pharmacopeia basket method and the FVDS method. Two dissolution media plans were implemented in FVDS i) Plan I involved dissolution in pH1.0 medium for 12 h; ii) Plan II initiated dissolution in pH1.0 medium for 1 h, followed by pH6.8 phosphate buffer for 11 h. The resulting dissolution data were fitted using classic mathematical models. Pixel information was further extracted from images obtained using FVDS and plotted over time. RESULTS: The basket method showed the cumulative dissolution of all three tablets in pH1.0, pH4.0 and water reached 80% within 6 h, but remained below 60% in the pH6.8 medium. The f2 values indicated CEC-2 was similar to CEC-1 in the pH4.0 medium, pH6.8 medium and water. Using FVDS with medium plan II, the cumulative dissolution of CEC-1 and CEC-2 reached about 80% showing similarity, while no similarity was observed between CEC-3 and CEC-1. The f2 factor of the percentage area change profiles also showed consistent results in the dissolution profile of medium plan II. However, FVDS with medium plan I cannot distinguish between CEC-2 and CEC-3. CONCLUSION: FVDS offers an alternative to traditional dissolution methods by integrating imaging analysis as a complementary tool to disintegration and dissolution testing methods.