Exploring space-energy matching via quantum-molecular mechanics modeling and breakage dynamics-energy dissipation via microhydrodynamic modeling to improve the screening efficiency of nanosuspension prepared by wet media milling.

The preparation of nanosuspensions by wet media milling is a promising technique that increases the bioavailability of insoluble drugs. The nanosuspension is thermodynamically unstable, where its stability might be influenced by the interaction energy between the stabilizers and the drugs after milling at a specific collision energy. However, it is difficult to screen the stabilizers and the parameters of milling accurately and quickly by using traditional analysis methods. Quantum-molecular mechanics and microhydrodynamic modeling can be applied to improve screening efficiency. Quantum-molecular mechanics model, which includes molecular docking, molecular dynamics simulations, and data on binding energy, provides insights into screening stabilizers based on their molecular behavior at the atomic level. The microhydrodynamic model explores the mechanical processes and energy dissipation in nanomilling, and even combines information on the mechanical modulus and an energy vector diagram for the milling parameters screening of drug crystals. These modeling methods improve screening efficiency and support screening theories based on thermodynamics and physical dynamics. However, how to reasonably combine different modeling methods with their theoretical characteristics and further multidimensional and cross-scale simulations of nanosuspension formation remain challenges.