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以棉子糖 - 氨基酸组合作为精细共喷雾干燥载体的茶碱可吸入粉末的优化、体外及计算机模拟表征

Optimization, In Vitro, and In Silico Characterization of Theophylline Inhalable Powder Using Raffinose-Amino Acid Combination as Fine Co-Spray-Dried Carriers.

作者信息

Party Petra, Soliman Lomass, Nagy Attila, Farkas Árpád, Ambrus Rita

机构信息

Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös Utca 6, 6720 Szeged, Hungary.

Department of Applied and Nonlinear Optics, HUN-REN Wigner Research Centre for Physics, Konkoly-Thege Miklós St. 29-33, 1121 Budapest, Hungary.

出版信息

Pharmaceutics. 2025 Apr 3;17(4):466. doi: 10.3390/pharmaceutics17040466.

DOI:10.3390/pharmaceutics17040466
PMID:40284461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12030175/
Abstract

: Dry powder inhalation is an attractive research area for development. Therefore, this work aimed to develop inhalable co-spray-dried theophylline (TN) microparticles, utilizing raffinose-amino acid fine carriers intended for asthma therapy. The study addressed enhancing TN's physicochemical and aerodynamic properties to ensure efficient lung deposition. : The process involves spray-drying each formulation's solution using a mini spray drier. A rigorous assessment was conducted on particle size distribution, structural and thermal analysis, morphology study, in vitro and in silico aerodynamic investigation, and aerodynamic particle counter in addition to the solubility, in vitro dissolution, and diffusion of TN. : The carriers containing leucine and glycine revealed superior characteristics (mass median aerodynamic diameter (MMAD): 4.6-5 µm, fine particle fraction (FPF): 30.6-35.1%, and amorphous spherical structure) as candidates for further development of TN-DPIs, while arginine was excluded due to intensive aggregation and hygroscopicity, which led to poor aerodynamic performance. TN co-spray-dried samples demonstrated fine micronized particles (D [0.5]: 3.99-5.96 µm) with predominantly amorphous structure (crystallinity index: 24.1-45.2%) and significant solubility enhancement (19-fold). Formulations containing leucine and leucine-glycine revealed the highest FPF (45.7-47.8%) and in silico lung deposition (39.3-40.1%), rapid in vitro drug release (100% within 10 min), and improved in vitro diffusion (2.29-2.43-fold), respectively. Moreover, the aerodynamic counter confirmed the development of fine microparticles (mean number particle size = 2.3-2.02 µm). : This innovative formulation possesses enhanced physicochemical, morphological, and aerodynamic characteristics of low-dose TN for local asthma treatment and could be applied as a promising carrier for dry powder inhaler development.

摘要

干粉吸入是一个具有吸引力的研发领域。因此，本研究旨在开发用于哮喘治疗的可吸入共喷雾干燥茶碱（TN）微粒，采用棉子糖 - 氨基酸作为精细载体。该研究致力于改善TN的物理化学和空气动力学性质，以确保在肺部有效沉积。

该过程包括使用小型喷雾干燥器对每种制剂的溶液进行喷雾干燥。除了TN的溶解度、体外溶出度和扩散外，还对粒径分布、结构和热分析、形态学研究、体外和计算机模拟空气动力学研究以及空气动力学颗粒计数器进行了严格评估。

含有亮氨酸和甘氨酸的载体表现出优异的特性（质量中值空气动力学直径（MMAD）：4.6 - 5 µm，细颗粒分数（FPF）：30.6 - 35.1%，以及无定形球形结构），可作为TN - DPI进一步开发的候选物，而精氨酸由于强烈聚集和吸湿性导致空气动力学性能不佳而被排除。TN共喷雾干燥样品显示出细的微粉化颗粒（D[0.5]：3.99 - 5.96 µm），主要为无定形结构（结晶度指数：24.1 - 45.2%），溶解度显著提高（约19倍）。含有亮氨酸和亮氨酸 - 甘氨酸的制剂分别显示出最高的FPF（45.7 - 47.8%）和计算机模拟肺部沉积（39.3 - 40.1%）、快速的体外药物释放（10分钟内约100%）以及改善的体外扩散（2.29 - 2.43倍）。此外，空气动力学计数器证实了细微粒的形成（平均颗粒尺寸 = 2.3 - 2.02 µm）。

这种创新制剂具有增强的物理化学、形态学和空气动力学特性，适用于低剂量TN的局部哮喘治疗，可作为干粉吸入器开发的有前景的载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/5558e34f6f80/pharmaceutics-17-00466-g013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/dbcf1663a5d5/pharmaceutics-17-00466-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/c16d851f7285/pharmaceutics-17-00466-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/37ef40683fec/pharmaceutics-17-00466-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/96a2145c16b9/pharmaceutics-17-00466-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/1f9c7f7c2318/pharmaceutics-17-00466-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b9/12030175/434e2c7ed7f4/pharmaceutics-17-00466-g012.jpg
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