School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States.
Department of Forensic Analytical Toxicology, China Medical University School of Forensic Medicine, Shenyang, China; Key Laboratory of Forensic Bio-evidence Sciences, Liaoning Province, China; China Medical University Center of Forensic Investigation, China.
Int J Pharm. 2022 Jun 25;622:121859. doi: 10.1016/j.ijpharm.2022.121859. Epub 2022 May 26.
The present study aimed to develop inhalable powder formulations with both dissolution enhancement and superior aerodynamic properties for potential pulmonary delivery of a poorly water-soluble drug, ivacaftor (IVA). The IVA-leucine (LEU) microparticle formulations were produced by spray drying and the physicochemical, aerosolization and cytotoxicity properties were characterized. Co-amorphous microparticle formulation was formed at the IVA: LEU 3:1 M ratio with hydrogen bond interactions as indicated by Fourier transform infrared spectroscopy (FTIR) results. Dissolution rate of the co-spray dried formulations was significantly improved as compared with the IVA alone or physical mixtures. The co-spray dried formulations exhibited > 80% fine particle fraction (FPF) and > 95% emitted dose percentage (ED) values respectively, with superior physical and aerosolization stability under 40℃ at 75% RH for 30 days. The laser scanning confocal microscopy results demonstrated that more IVA was uptake by Calu-3 cell lines for the co-spray dried formulation. In summary, our results demonstrated that co-spray drying IVA with LEU could achieve enhanced in vitro release and superior aerodynamic properties for pulmonary delivery of IVA.
本研究旨在开发具有增强溶解性能和卓越空气动力学性能的可吸入粉末制剂，以用于潜在的肺部输送一种水溶性差的药物，即依伐卡托（IVA）。通过喷雾干燥制备了 IVA-亮氨酸（LEU）微颗粒制剂，并对其理化性质、气溶胶化特性和细胞毒性进行了表征。共无定形微颗粒制剂在 IVA: LEU 3:1 M 比例下形成，氢键相互作用如傅里叶变换红外光谱（FTIR）结果所示。与单独的 IVA 或物理混合物相比，共喷雾干燥制剂的溶解速率显著提高。共喷雾干燥制剂的细颗粒分数（FPF）>80%，发射剂量百分比（ED）>95%，在 40℃、75%相对湿度下 30 天内具有优异的物理和空气动力学稳定性。激光扫描共聚焦显微镜结果表明，共喷雾干燥制剂中更多的 IVA 被 Calu-3 细胞系摄取。总之，我们的结果表明，将 LEU 与 IVA 共喷雾干燥可以实现 IVA 的体外释放增强和肺部输送的卓越空气动力学性能。
