Molecular simulations for amorphous drug formulation: Polymeric matrix properties relevant to hot-melt extrusion

In the present study molecular modelling was used to evaluate polymeric drug carrier matrix properties suitable for hot-melt extrusion (HME). Specifically, the effect of three commonly used plasticizers, namely, citric acid (CA), triethyl citrate (TEC) and polyethylene glycol (PEG), on Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, SOL) properties were evaluated with the aid of classical molecular dynamics (MD) and docking simulations. Differential scanning calorimetry (DSC) and ATR-FTIR spectroscopy of polymer-plasticizer mixtures were used to experimentally verify the in silico predictions. Computed Tg value by MD simulations for SOL was in reasonable agreement with the experimentally determined Tg value (72.0 vs. 69.4 °C, for MD and DSC measurement, respectively). Solubility parameter calculations with the aid of MD simulations along with calculated molecular lipophilicity potential interaction (MLPI) scores based on molecular docking, suggested component miscibility only in the case of SOL and PEG. This was verified by a positive deviation of the Tg values determined by DSC, compared to the Gordon-Taylor theoretical predictions. Additionally, the calculated MLPI scores suggested strong interactions between SOL and PEG, verified also by ATR-FTIR. Finally, MD simulations of the hydration process suggested strong hydrogen bonding between SOL - CA, and CA - water molecules.