Predictive dissolution modeling across USP apparatuses I, II, and III.

Abstract

Dissolution testing provides in vitro drug release characterization and serves a critical role in the development of solid oral dosage forms. The most common dissolution apparatuses are the USP apparatuses I and II, for which in silico tools have been previously developed for predictive dissolution modeling (PDM). While apparatuses I and II serve the greater volume of projects, apparatus III offers higher agitation levels and multivessel capabilities, which is critical for certain projects, and the physics of which have not been previously characterized. To mitigate that knowledge gap, the present work characterizes the transport physics and thermodynamics of dissolution apparatus III, such that a 1-D model is established and validated which scales release kinetics with agitation level across apparatuses I, II, and III. The resulting PDM is calibrated with at least two dissolution experiments at different agitation levels, for a particular formulation-medium combination, after which release kinetics are predicted within the design spaces of the three apparatuses. Calibration data can come from experiments using a single apparatus or different apparatuses, while still predicting across all three apparatuses. Erosion-based formulations are used for validation. Additionally, apparatus III vessel residence time analysis is demonstrated.