Spray dried inhalable ivacaftor co-amorphous microparticle formulations with leucine achieved enhanced in vitro dissolution and superior aerosol performance.
Spray dried inhalable ivacaftor co-amorphous microparticle formulations with leucine achieved enhanced in vitro dissolution and superior aerosol performance.
复制标题
DOI：
10.1016/j.ijpharm.2022.121859
复制
发表时间：
2022-06-25
影响因子：
5.8
通讯作者：
Zhou, Qi Tony
中科院分区：
文献类型：
--
作者：
Guan, Jian;Yuan, Huiya;Yu, Shihui;Mao, Shirui;Zhou, Qi Tony
本研究旨在开发具有溶出增强和上级空气动力学特性的可吸入粉末制剂，用于水溶性差的药物依伐卡托（IVA）的潜在肺部递送。通过喷雾干燥制备IVA-亮氨酸（LEU）微粒制剂，并表征其物理化学、气溶胶化和细胞毒性性质。如傅里叶变换红外光谱（FTIR）结果所示，以IVA：LEU 3：1摩尔比形成具有氢键相互作用的共无定形微粒制剂。与单独的IVA或物理混合物相比，共喷雾干燥制剂的溶出速率显著提高。共喷雾干燥的制剂分别表现出>80%的细颗粒分数（FPF）和> 95%的发射剂量百分比（艾德）值，在40 ℃和75%RH下持续30天具有上级物理和雾化稳定性。激光扫描共聚焦显微镜结果表明，对于共喷雾干燥制剂，Calu-3细胞系摄取更多的IVA。总之，我们的研究结果表明，共喷雾干燥IVA与LEU可以实现增强的体外释放和上级空气动力学性质的肺递送IVA。
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 molar 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°C 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.
登录
查看更多内容
影响因子：
5.8
作者：
Li, Liang;Leung, Sharon Shui Yee;Chan, Hak-Kim
通讯作者：
Chan, Hak-Kim
影响因子：
5.8
作者：
Momin, Mohammad A. M.;Sinha, Shubhra;Das, Shyamal C.
通讯作者：
Das, Shyamal C.
DOI：
10.5863/1551-6776-18.1.8
发表时间：
2013-01-01
期刊：
The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG
影响因子：
--
作者：
Condren, Michelle E;Bradshaw, Marquita D
通讯作者：
Bradshaw, Marquita D
影响因子：
5.8
作者：
Chai, Guihong;Park, Heejun;Zhou, Qi (Tony)
通讯作者：
Zhou, Qi (Tony)
影响因子：
3.4
作者：
Hashem, Fahima M.;Abd Allah, Fathy I.;Hassan, Abdelsabour A. A.
通讯作者：
Hassan, Abdelsabour A. A.