Diffusivity of α-, β-, γ-cyclodextrin and the inclusion complex of β-cyclodextrin: Ibuprofen in aqueous solutions; A molecular dynamics simulation study

Cyclodextrins (CDs) are widely used in drug delivery, catalysis, food and separation processes. In this work, a comprehensive simulation study on the diffusion of the native α-, β- and γ-CDs in aqueous solutions is carried out using Molecular Dynamics simulations. The effect of the system size on the computed self-diffusivity is investigated and it is found that the required correction can be as much as 75% of the final value. The effect of the water force field is examined and it is shown that the q4md-CD/TIP4P/2005 force field combination predicts the experimentally measured self-diffusion coefficients of CDs very accurately. The self-diffusion coefficients of the three native CDs were also computed in aqueous-NaCl solutions using the Joung and Cheatham (JC) and the Madrid-2019 force fields. It is found that Na⁺ ions have higher affinity towards the CDs when the JC force field is used and for this reason the predicted diffusivity of CDs is lower compared to simulations using the Madrid-2019 force field. As a model system for drug delivery and waste-water treatment applications, the diffusion of the β-CD:Ibuprofen inclusion complex in water is studied. In agreement with experiments for similar components, it is shown that the inclusion complex and the free β-CD have almost equal self-diffusion coefficients. Our analysis revealed that this is most likely caused by the almost full inclusion of the ibuprofen in the cavity of the β-CD. Our findings show that Molecular Dynamics simulation can be used to provide reasonable diffusivity predictions, and to obtain molecular-level understanding useful for industrial applications of CDs.