Respiratory Technology, Woolcock Institute of Medical Research, Glebe, Sydney, NSW 2037, Australia.
School of Chemical Engineering, University of New South Wales, Sydney, Australia.
Int J Pharm. 2022 Aug 25;624:121989. doi: 10.1016/j.ijpharm.2022.121989. Epub 2022 Jul 6.
This study aims to investigate the effect of physicochemical properties and aerosol performance of two (2FN) and three-fluid nozzles (3FN) on the inhalable co-formulation of tobramycin and diclofenac dry powders. Combination formulations of tobramycin and diclofenac at 2:1 and 4:1 w/w ratios were prepared at a laboratory scale using a spray dryer in conjunction with a 2FN or 3FN. Powder size, morphology, solid-state characteristics, and aerodynamic and dissolution properties were characterised. The nozzle types and the formulation composition influenced the yield, particle size, solid-state properties, aerosolization behaviour and dissolution of the co-spray dried formulations. In particular, using the 2FN the co-spray dried formulation of tobramycin and diclofenac at 2:1 w/w showed smaller particle size (D50, 3.01 ± 0.06 μm), high fine particle fractions (FPF) (61.1 ± 3.6% for tobramycin and 65.92 ± 3 for diclofenac) and faster dissolution with approx. 70% diclofenac released within 3 h and approx. 90% tobramycin was released within 45 min. However, the 3FN for the co-spray dried formulation of tobramycin and diclofenac at a 2:1 w/w ratio showed a larger particle size (D50, 3.42 ± 0.02 μm), lower FPF (40.6 ± 3.4% for tobramycin and 36.9 ± 0.84 for diclofenac) and comparative slower dissolution with approx. 60% diclofenac was released within 3 h and 80% tobramycin was released within 45 min. A similar trend was observed when the tobramycin to diclofenac ratio was increased to 4:1 w/w. Overall results suggest that spray drying with 2FN showed a superior and viable approach to producing excipients-free inhalable co-spray dried formulations of tobramycin and diclofenac. However, the formulation produced using the 3FN showed higher enrichment of hydrophobic diclofenac and an ability to control the tobramycin drug release in vitro.
本研究旨在探讨两种（2FN）和三种流体喷嘴（3FN）的物理化学性质和气溶胶性能对妥布霉素和双氯芬酸钠干粉可吸入共制剂的影响。采用喷雾干燥法，在实验室规模下，使用 2FN 或 3FN 联合制备妥布霉素和双氯芬酸钠 2:1 和 4:1w/w 的组合配方。对粉末粒径、形态、固态特性、空气动力学和溶解性能进行了表征。喷嘴类型和配方组成影响共喷雾干燥配方的收率、粒径、固态特性、气溶胶化行为和溶解。特别是使用 2FN，妥布霉素和双氯芬酸钠 2:1w/w 的共喷雾干燥配方粒径较小（D50，3.01±0.06μm），细颗粒分数（FPF）较高（妥布霉素 61.1±3.6%，双氯芬酸钠 65.92±3%），溶解速度较快，约 3h 内释放约 70%的双氯芬酸钠，约 45min 内释放约 90%的妥布霉素。然而，3FN 用于妥布霉素和双氯芬酸钠 2:1w/w 的共喷雾干燥配方的粒径较大（D50，3.42±0.02μm），FPF 较低（妥布霉素 40.6±3.4%，双氯芬酸钠 36.9±0.84%），溶解速度较慢，约 3h 内释放约 60%的双氯芬酸钠，约 45min 内释放约 80%的妥布霉素。当妥布霉素与双氯芬酸钠的比例增加到 4:1w/w 时，观察到类似的趋势。总体结果表明，使用 2FN 喷雾干燥是生产妥布霉素和双氯芬酸钠无赋形剂可吸入共喷雾干燥配方的一种优越且可行的方法。然而，使用 3FN 制备的配方显示出更高的疏水性双氯芬酸钠富集能力，并能够控制体外妥布霉素药物释放。
