Molecular modelling and simulation of fusion-based amorphous drug dispersions in polymer/plasticizer blends

A realistic molecular description of amorphous drug-polymer-plasticizer matrices, suitable for the preparation of amorphous solid dispersions (ASDs) with the aid of fusion-based techniques, was evaluated. Specifically, the incorporation of two model drugs (i.e. ibuprofen, IBU, and carbamazepine, CBZ) having substantially different thermal properties and glass forming ability, on the molecular representation of polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (SOL)/polyethylene glycol (PEG, working as a plasticizer) molecular and thermal properties were evaluated with the aid of classical molecular dynamics (MD) and docking simulations. Results showed good agreement between molecular modelling estimations and experimentally determined properties. Specifically, the computed Tg values that resulted from MD simulations for IBU-SOL/PEG and CBZ-SOL/PEG (53.8 and 54.2 °C, respectively) were in reasonable agreement with the corresponding values resulting from differential scanning calorimetry (DSC) measurements (49.8 and 50.1 °C), while both molecular modelling and experimental obtained results suggested miscibility among system components. Additionally, interactions between CBZ and SOL observed during MD simulations were verified by FTIR analysis, while MD simulations of the hydration process suggested strong molecular interactions between IBU-SOL and CBZ-SOL.