文献分享 I 阿司匹林可吸入粉末的制备、性能及体内外研究

            Aspirin is an antiplatelet agglutinating drug used clinically for the prevention and treatment of angina pectoris, myocardial infarction, and cerebral thrombosis. In this study, aspirin inhalable powder was prepared by ultrasound-intensified anti-solvent crystallization (UIAC) and developed for rapid antiplatelet aggregation, which could reduce the dose and gastrointestinal irritation. The particle size distribution, morphology, density, fluidity, and in vitro aerodynamic performance of the as-prepared powders were systematically evaluated. Meanwhile, machine learning methodology, specifically utilizing the Decision Tree Regressor in conjunction with Shapley Value analysis, was applied to elucidate the influence of critical process parameters within the production process. The powder flowability could be improved by the addition of excipients L150 and L-leucine (Leu). The value of fine particle fraction (FPF) increased from 10.40 % to 45.86 % when adding L150 (60 %, w/ w) and Leu (5 %, w/w). The cytotoxicity study of aspirin inhalable powder was performed at cellular level, and demonstrated aspirin powder had no significant toxic effect. The Calu-3 cell monolayer interfaced to simulate lung epithelial tissue, demonstrated the high permeability of inhalable powder in lung. Pharmacokinetics were investigated in healthy rats, compared with oral administration, the Tmax of inhale administration (10 min) was significantly shorter than oral administration (30 min), and the AUC was 1.91 times higher than that of the oral administration, demonstrating that pulmonary drug delivery accelerated the absorption and increased the bioavailability of aspirin.

              阿司匹林是一种抗血小板凝集药物，临床上用于预防和治疗心绞痛、心肌梗死和脑血栓形成。在本研究中，通过超声强化反溶剂结晶法制备了阿司匹林可吸入粉末，并将其用于快速抑制血小板聚集，从而能够减少用药剂量并降低对胃肠道的刺激作用。对所制备粉末的粒度分布、形态、密度、流动性以及体外气动性能进行了系统评估。同时采用机器学习方法，特别是结合决策树回归器与Shapley值分析，来阐明生产过程中关键工艺参数的影响。通过添加辅料 L150 和 L-亮氨酸（Leu），粉末的流动性能够得到改善。当加入 L150（60%，质量百分比）和亮氨酸（5%，质量百分比）后，颗粒分数（FPF）的数值从 10.40% 增加到了 45.86%。在细胞水平上进行了阿司匹林可吸入粉末的细胞毒性研究，结果表明阿司匹林粉末没有明显的毒性作用。使用Calu-3细胞单层界面模拟肺上皮组织，证明了可吸入粉末在肺中的高渗透性。对健康大鼠进行了药代动力学研究，与口服给药相比，吸入给药（10 分钟）的达峰时间显著短于口服给药（30 分钟），且曲线下面积（AUC）是口服给药的 1.91 倍，这表明肺部给药加速了药物吸收并提高了生物利用度。

Aspirin Inhalable powder Ultrasound-intensified antisolvent crystallization Machine learning Pulmonary drug delivery

阿司匹林、可吸入粉末、超声波强化反溶剂结晶、机器学习、肺部给药

2025-US-Preparation of aspirin inhalable powder by ultrasound-intensified anti-solvent crystallization for pulmonary drug delivery.pdf 。