Insights on Molecular Interaction between Polymer and Poorly Water-Soluble Loratadine in Solid Dispersion from Molecular Dynamics and Experiments.

Abstract

This study aims to employ molecular dynamics (MD) methods to predict the miscibility and molecular interactions between loratadine (LOR) and polymers, thereby designing drug formulations with enhanced water solubility. The research seeks to improve formulation design efficiency and accelerate the drug development process. A viable approach to enhance the solubility of poorly soluble drugs involves creating solid dispersions (SDs) with hydrophilic polymers. However, the specific intermolecular interactions within this system warrant further investigation. In this study, MD simulations were conducted to assess the molecular miscibility and interactions between LOR and 4 polymers. Then, the simulation results were verified by physical experiments. The findings demonstrate that LOR exhibits substantial miscibility with these polymers. Among the 2 drug loading ratios, S4 and S7 exhibited the strongest interactions, respectively. The solubility experiment also confirmed this result. It is confirmed that MD can be used to predict the formation of SDs, and this method can also predict the water solubility of the system, underscoring the utility of MD in advancing the development of SDs.