Alyami Mohammad H, Dahmash Eman Zmaily, Ali Dalia Khalil, Alyami Hamad S, AbdulKarim Hussien, Alsudir Samar A
Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia.
Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan.
Pharmaceuticals (Basel). 2022 Mar 8;15(3):321. doi: 10.3390/ph15030321.
One of the key challenges in developing a dry powder inhaler (DPI) of an inhalable potent fixed-dose combination (FDC) is the ability of the formulation to generate an effective and reproducible aerosol able to reach the lower parts of the lungs. Herein, a one-step approach is presented to expedite the synthesis of nanoaggregates made from a biocompatible and biodegradable polyamide based on L-lysine amino acid employing market-leading active pharmaceutical ingredients (fluticasone propionate (FP) and salmeterol xinafoate (SAL)) for the management of asthma. The nanoaggregates were synthesized using interfacial polycondensation that produced nanocapsules with an average particle size of 226.7 ± 35.3 nm and zeta potential of -30.6 ± 4.2 mV. Differential scanning calorimetric analysis and x-ray diffraction, as well as scanning electron microscopy of the produced FDC, revealed the ability of the produced nanocapsules to encapsulate the two actives and display the best aerodynamic performance. The FDC nanocapsules displayed 88.5% and 98.5% of the emitted dose for FP and SAL, respectively. The fine particle fraction of the nominated dose was superior to the marketed product (Seretide Diskus, Brentford, United Kingdom). The in-vitro release study showed an extended drug release profile. Our findings suggest that nanoaggregates using polyamides based on L-lysine and interfacial polycondensation can serve as a good platform for pulmonary drug delivery of FDC systems.
开发可吸入强效固定剂量组合（FDC）的干粉吸入器（DPI）的关键挑战之一是制剂产生能够到达肺部下部的有效且可重现气雾剂的能力。本文提出了一种一步法，以加速由基于L-赖氨酸氨基酸的生物相容性和可生物降解聚酰胺制成的纳米聚集体的合成，该聚酰胺采用市场领先的活性药物成分（丙酸氟替卡松（FP）和昔萘酸沙美特罗（SAL））来治疗哮喘。使用界面缩聚合成纳米聚集体，产生平均粒径为226.7±35.3nm且ζ电位为-30.6±4.2mV的纳米胶囊。对所制备的FDC进行差示扫描量热分析、X射线衍射以及扫描电子显微镜分析，结果表明所制备的纳米胶囊能够包封两种活性成分并展现出最佳的空气动力学性能。FDC纳米胶囊的FP和SAL的 emitted dose分别为88.5%和98.5%。指定剂量的细颗粒分数优于市售产品（英国布伦特福德的舒利迭准纳器）。体外释放研究显示出延长的药物释放曲线。我们的研究结果表明，基于L-赖氨酸的聚酰胺和界面缩聚的纳米聚集体可作为FDC系统肺部给药的良好平台。
