Abstract: Pharmaceutical excipients, also known as "inactive ingredients", are other components in pharmaceutical preparations besides active ingredients. Pharmaceutical excipients are an indispensable and important component in pharmaceutical preparations, and they can significantly affect the release performance of pharmaceutical preparations by forming drug excipient interactions, which is crucial for the effectiveness and safety of pharmaceutical preparations. The development of high-end preparations also puts higher requirements on excipients. Therefore, it is necessary to analyze the mechanism by which excipients in high-end formulations affect the quality of drug formulations. Although the addition of excipients can enhance the release and bioavailability of active ingredients in drugs, improve and maintain drug stability, achieve controllable targeted release of drugs, and act as masking and sweeteners to improve drug bioavailability and patient adherence, more and more studies have shown that excipients can produce physiological activity and affect drug pharmacokinetics, causing adverse reactions such as allergies or intolerance. Large amounts of ingested excipients may also inhibit drug release by interacting with drugs. This review briefly describes the impact mechanisms of commonly used excipients on drug release from the perspective of drug excipient interactions, such as polymers and mesoporous silica. At the same time, it summarizes the research progress of excipient controlled drug release mechanisms based on mathematical models, molecular simulations, and machine learning methods based on drug excipient interactions, and proposes the development direction of future pharmaceutical excipient database establishment for high-throughput screening of suitable pharmaceutical excipients. Determine the optimal drug loading and excipient addition, and provide data support and theoretical guidance for selecting appropriate production processes.

Key words: drug-excipient interaction, drug release rate, mechanism model, molecular simulation, machine learning

摘要： 药用辅料称为“非活性成分”，是药物制剂中除药物活性成分以外的其他组分，药用辅料是药物制剂中不可或缺的重要组成部分，其会通过形成药物-辅料相互作用等方式显著影响药物制剂的释放性能，对于药物制剂的有效性和安全性影响至关重要，高端制剂的发展也对辅料提出更高要求，因此需要剖析高端制剂中辅料对药物制剂质量影响的机制。辅料的加入可以增强药物活性成分的释放度和生物利用度、提高并维持药物的稳定性、实现药物的可控靶向释放以及充当掩味剂和甜味剂，提高药物的生物利用度和患者的服药依从性，但愈来愈多的研究表明辅料会产生生理活性而影响药物药代动力学，引起过敏或不耐受等不良反应，大量摄入辅料也可能通过与药物形成相互作用从而抑制药物释放。本工作从药物-辅料相互作用角度，简述了常用的辅料对药物释放的影响机制，如聚合物、介孔二氧化硅，同时归纳了基于药物-辅料相互作用的数学模型、分子模拟及机器学习等手段深入揭示辅料调控药物释放机制的研究进展，并提出未来药用辅料数据库建立的发展方向，为高通量筛选合适的药用辅料、确定最佳载药量和辅料添加量以及选择合适生产工艺提供数据支撑和理论指导。

关键词: 药物-辅料相互作用, 药物释放速率, 机制模型, 分子模拟, 机器学习