Impact Of Structural Binding Energies On Dissolution Rates For Single Faceted-Crystals

This study investigates the effect of solid-state intermolecular binding energies on the dissolution rates of single faceted-crystals. The nonsteroidal anti-inflammatory drug ibuprofen is employed in a 95% v/v ethanol:water solution as a model system for single-crystal dissolution experiments in a dissolution cell at undersaturation ranging from 1.36% to 8.67%. In vitro dissolution of the ibuprofen crystals is quantified by capturing images during the dissolution process at fixed time intervals using a camera mounted on an inverted optical microscope. The regression rate of crystal faces with time is measured by an image analysis. VisualHabit software is used for a prediction of the crystal morphology and to characterize the intermolecular binding energies in the solid-state structure of the ibuprofen crystals to predict relative, face-specific dissolution rates. The relative face-specific dissolution rates of ibuprofen crystal calculated based on binding energies suggest that the face (011) dissolves faster than face (002). The experimental results on face-specific dissolution rates of single ibuprofen crystals reveal that the dissolution rates of faces (011) and (002) change nonlinearly as a function of undersaturation. The binding energy model is critically evaluated for performance as confronted with the experimental measurements. The binding energy model suggests a pathway to understand dissolution at the microscopic level and to design a crystal morphology for regulating bioavailability optimally during dissolution processes.