Hydrodynamic Studies of Cocrystal under Nonsink Dissolution on Orbital Shaker

Abstract

The dissolution behavior of pharmaceutical cocrystals, particularly under nonsink conditions, is influenced by operational parameters such as Erlenmeyer flask size and rotation speed. This study investigates the hydrodynamic impacts of these variables on the dissolution of lamotrigine-nicotinamide (LAM-NIC) cocrystals using experimental and computational approaches. Dissolution experiments were conducted in orbital shakers with 125 and 250 mL Erlenmeyer flasks at 50, 100, and 150 rpm. The results showed that the Erlenmeyer flask size and rotation speed significantly affect the dissolution profile, with the 250 mL Erlenmeyer flask at 100 rpm providing the most favorable conditions among those investigated for revealing the supersaturated state. Computational fluid dynamics (CFD) simulations modeled the fluid dynamics within the flasks, providing insights into the velocity and strain rate profiles under different conditions. A higher tangential velocity and strain rate at 100 rpm correlated with enhanced cocrystal dissolution in the 250 mL Erlenmeyer flask, whereas the smaller flask showed a limited variation across rotation speeds. These findings emphasize the importance of hydrodynamic conditions in dissolution studies and support the development of standardized methodologies for assessing cocrystal performance under nonsink conditions. This research contributes to optimizing the design of supersaturating drug delivery systems and understanding the interplay between the hydrodynamics and cocrystal behavior.