Molecular Dynamic Approach to Predict the Miscibility of Excipients for Lipid-based Formulations.

Abstract This research work sought to investigate the miscibility of various excipients with Nebivolol hydrochloride (NBV) to develop stable lipid-based nanoparticles. The miscibility of NBV with excipients such as Glyceryl Mono Oleate (GMO), VIT-E TPGS and Poloxamer 407 was predicted using molecular simulation. The miscibility predicted by in-silico approach was corroborated with a thermogram obtained from Differential Scanning Calorimetry (DSC). Desmond MD engine using OPLS-3e force field was used to perform molecular dynamic (MD) simulations. The cohesive energy density and the solubility parameters (δ) were determined for all the compounds. Solubility parameters computed from the simulation indicate that the mixture of NBV/GMO and NBV/VITE-TPGS are miscible with each other. The miscibility is determined by the difference in solubility parameter between drug and carrier. DSC thermogram observations have substantiated the miscibility of NBV /GMO, NBV/Poloxamer 407 and NBV/VITE-TPGS. This finding indicates that Nebivolol hydrochloride is soluble in GMO and this combination is further miscible with Poloxamer 407. NBV/POLOXAMER 407 is predicted as immiscible. With this study, we report that the molecular dynamic simulation can potentially be used to understand the molecular level insights to develop the thermodynamically stable formulation.