2022 Annual Meeting

Molecular Dynamics Simulations of Cannabidiol Amorphous Solid Dispersions

Molecular Dynamics Simulations of Cannabidiol Amorphous Solid Dispersions
October 14, 2022
Stephanie Monson

ABSTRACT
Cannabidiol (CBD) has been gaining popularity as a therapeutic, targeting diseases such as
epilepsy and alzheimers. Like many other small molecule therapeutics, it has low solubility
and bioavailability [1]. Amorphous solid dispersions (ASD) are a formulation in which a small
molecule API (active pharmaceutical ingredient) with low bioavailability is mixed with an amor-
phous polymer matrix to improve stability and solubility. Only recently have studies begun in-
vestigating formulation methods for CBD, including amorphous solid dispersions. As is the case
with many other APIs, CBD aqueous stability can significantly increase in an amorphous polymer
formulation [2].
An understanding of principal API-carrier interactions, solubility, and dissolution contributes
to the efficient development of drug formulations. Molecular dynamics simulations are a method-
ology utilizing Newton’s laws of motion and force field energy parameterization to provide data
on particle position, velocities, and energies at timesteps on the scale of femto- (10−15) seconds.
These simulations can provide understanding of the molecular-level interactions which contribute
to solubility and dissolution and cannot be elucidated experimentally. Molecular dynamics sys-
tems have recently been developed to understand and optimize amorphous solid dispersions for a
variety of APIs [3]. However, these simulations have not yet been utilized to understand ASDs for
CBD therapeutics. The present study develops a molecular dynamics simulation model to under-
stand and optimize molecular-level interactions and solubility of CBD ASDs. This includes the
computationally-based development of amorphous systems of CBD, polymers, and CBD-polymer
mixtures at varying concentrations, which are run through molecular dynamics simulations. The
data from simulations are used to compute theoretical parameters for the mixture, such as glass
transition temperature, solubility parameters, and radial distribution function. The present study
contributes to both the development of effective CBD therapeutics and the further development of
molecular dynamics simulation models for drug formulations.