ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

摘要

介绍：通过湿介质研磨制备纳米混悬剂是一种很有前途的技术，可以提高不溶性药物的生物利用度。纳米混悬液在热力学上不稳定，其稳定性可能受到在特定碰撞能量下研磨后稳定剂和药物之间的相互作用能的影响。然而，传统的分析方法难以准确、快速地筛选稳定剂和铣削参数。可以应用量子分子力学和微流体动力学模型来提高筛选效率。

涵盖的领域：量子分子力学模型，包括分子对接、分子动力学模拟和结合能数据，提供了基于原子水平分子行为筛选稳定剂的见解。微流体动力学模型探索了纳米研磨中的机械过程和能量耗散，甚至结合了机械模量和能量矢量图的信息，用于药物晶体的研磨参数筛选。

专家意见：这些建模方法提高了筛选效率，支持了基于热力学和物理动力学的筛选理论。然而，如何将不同的建模方法与其理论特性合理结合，进一步多维、跨尺度模拟纳米悬浮液的形成仍然是一个挑战。