Computational Insights into the Atomic-Scale Structure and Interactions Underlying the Stability and Performance of Amorphous Solid Dispersions of Cannabidiol

Abstract

Cannabidiol (CBD) has been gaining popularity as a therapeutic, targeting diseases such as epilepsy and Alzheimer’s. Like many other small molecule drugs, CBD has low solubility and bioavailability, meaning that it is difficult for the drug molecule to absorb into the bloodstream to provide its positive therapeutic effects. Amorphous Solid Dispersions (ASD) are a formulation in which a small molecule Active Pharmaceutical Ingredient (API) is mixed with an amorphous polymer matrix to improve stability and solubility. Understanding the principal API-carrier interactions governing ASD stability and solubility contributes to efficient optimization and design of formulations. Only recently have studies begun investigating 1.) formulation methods for CBD, including ASDs, and 2.) the atomic-level behavior and interactions of ASDs in general. This study is thus one of the few to utilize Molecular Dynamics (MD) simulations to gain insights into atomic-level behavior of ASDs, and it does so with the case study of a drug which is in early stages of development for efficient formulations. This study performs MD simulations of CBD ASDs with poly-vinylpyrrolidone (PVP), poly-methyl methacrylate (PMMA), and poly-vinylpyrrolidone/vinyl acetate (PVPVA). Through computational analysis of distribution profiles, glass transition temperature, hydrogen bonds, and free energy, this study connects physical ASD behavior to molecular-level properties to guide future design of polymeric systems.