Studies of Bicalutamide–Excipients Interaction by Combination of Molecular Docking and Molecular Dynamics Simulation

While the effects of hydrophilic excipients in enhancing the dissolution rate of water-insoluble drugs have been validated, the underlying mechanism remains poorly understood, particularly at a molecular level. In this work, a combination of docking calculations and MD simulations was applied to investigate the molecular interactions between bicalutamide (BIC) and each of three excipients: lactose (LAC), hydroxypropyl methylcellulose (HPMC), and mannitol (MAN). The calculated results indicated that BIC interacted with HPMC and MAN mainly by Lennard-Jones (LJ) interactions but with LAC mainly by Coulomb (Coul) interactions. There was no hydrogen bond formed between BIC and excipient. It was shown that BIC/LAC had the biggest total solvent accessible surface area with the biggest hydrophilic area and formed the most hydrogen bonds between excipient and water. In addition to the structure analyses, BIC/LAC had both the lowest interaction energy between BIC and excipient and the lowest interaction energy between BIC/excipient and water. All these led to the best dissolution performance of BIC/LAC, which could correspond to the experimental results of dissolution test. The present study suggests that a combination of docking calculations and MD simulations, which aims at complementing the experimental work, could provide a molecular insight into the interaction between drug and excipient. It also holds the great potential to simplify the optimization process of drug delivery system and reduce both time and costs.