Hydrogen Bonding Principle-Based Molecular Design of a Polymer Excipient and Impacts on Hydrophobic Drug Properties: Molecular Simulation and Experiment

Abstract

Although some commercial excipients for improving the solubility of highly crystalline drugs are widely used, they still cannot cover all types of hydrophobic drugs. In this regard, with phenytoin as the target drug, related molecular structures of polymer excipients were designed. The optimal repeating units of NiPAm and HEAm were screened out through quantum mechanical simulation and Monte Carlo simulation methods, and the copolymerization ratio was also determined. Using molecular dynamics simulation technology, it was confirmed that the dispersibility and intermolecular hydrogen bonds of phenytoin in the designed copolymer were better than those in the commercial PVP materials. At the same time, the designed copolymers and solid dispersions were also prepared during the experiment, and the improvement of their solubility was confirmed, which is in accordance with the simulation predictions. The new ideas and simulation technology may be used for drug modification and development.

Using Polymers as Crystal Inhibitors to Prevent the Crystallization of the Rotigotine Patch

“…If the binding free energy is positive, external energy may be required during the binding process between the drug and the polymer molecule. If the binding free energy is negative, there is the possibility of docking between drug and polymer molecule, and the lower the binding free energy is, more stable the bond between drug and polymer molecule is [36]. As shown in Table 2, the binding free energies between ROT and polymer were all negative.…”

Interdisciplinary advances reshape the delivery tools for effective NASH treatment

“…Upon to now, molecular simulation has successfully aided the design of novel drug-excipient pair, such as polymers NiPAm and HEAm (excipient) for phenytoin (drug) through quantum mechanical simulation and Monte Carlo simulation methods [ 175 ]; capsaicin (drug)-montmorillonite (excipient) [ 176 ]; amphotericin B- polyoxyl-40-stearate [ 177 ]; myricetin-poly (vinyl pyrrolidone) [ 178 ], etc. The reliability of computational prediction has been validated by follow-up experiments, indicating the promising perspective of its application in disease treatment.…”

Improving Interfacial Adhesion of Graphite/Epoxy Composites by Surface Functionalization

“…These issues can lead to gas leakage in the fuel cell, reducing efficiency and stability. , Therefore, a critical aspect of combining graphite and epoxy resin is establishing strong interfacial adhesion . The interface properties of G/EP have been enhanced through methods including interfacial bonding, resin modification, and interface grafting . One of the most effective methods for improving interfacial adhesion is appropriately modifying the graphite surface. , To that end, functional groups have been incorporated onto the graphite surface to modify the interface between graphite and resin.…”

“…11,12 Therefore, a critical aspect of combining graphite and epoxy resin is establishing strong interfacial adhesion. 13 The interface properties of G/EP have been enhanced through methods including interfacial bonding, 14 resin modification, 15 and interface grafting. 16 One of the most effective methods for improving interfacial adhesion is appropriately modifying the graphite surface.…”