Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Ha'il, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Int J Pharm. 2024 Apr 25;655:123966. doi: 10.1016/j.ijpharm.2024.123966. Epub 2024 Mar 5.
The potential of fine excipient materials to improve the aerodynamic performance of carrier-based dry powder inhalation (DPI) formulations is well acknowledged but not fully elucidated. To improve the understanding of this potential, we studied two fine excipient materials: micronized lactose particles and silica microspheres. Inhalation formulations, each composed of a coarse lactose carrier, one of the two fine excipient materials (0.0-15.0 % w/w), and a spray-dried drug (fluticasone propionate) material (1.5 % w/w) were prepared. The physical structure, the flow behavior, the aerosolization behavior, and the aerodynamic performance of the formulations were studied. The two fine excipient materials similarly occupied carrier surface macropores. However, only the micronized lactose particles formed agglomerates and appeared to increase the tensile strength of the formulations. At 2.5 % w/w, the two fine excipient materials similarly improved drug dispersibility, whereas at higher concentrations, the micronized lactose material was more beneficial than the silica microspheres. The findings suggest that fine excipient materials improve drug dispersibility from carrier-based DPI formulations at low concentrations by filling carrier surface macropores and at high concentrations by forming agglomerates and/or enforcing fluidization. The study emphasizes critical attributes of fine excipient materials in carrier-based DPI formulations.
精细赋形剂材料改善载体干粉吸入剂（DPI）制剂空气动力学性能的潜力已得到充分认可，但尚未完全阐明。为了更好地理解这种潜力，我们研究了两种精细赋形剂材料：微粉化乳糖颗粒和硅胶微球。制备了包含粗乳糖载体、两种精细赋形剂材料（0.0-15.0%w/w）之一和喷雾干燥药物（丙酸氟替卡松）材料（1.5%w/w）的吸入制剂。研究了制剂的物理结构、流动行为、雾化行为和空气动力学性能。这两种精细赋形剂材料相似地占据了载体表面大孔。然而，只有微粉化乳糖颗粒形成了团聚体，似乎增加了制剂的拉伸强度。在 2.5%w/w 时，两种精细赋形剂材料相似地改善了药物的分散性，而在较高浓度下，微粉化乳糖材料比硅胶微球更有利。研究结果表明，精细赋形剂材料通过填充载体表面大孔和形成团聚体和/或强制流化，在低浓度下改善了载体 DPI 制剂中药物的分散性，在高浓度下改善了药物的分散性。该研究强调了精细赋形剂材料在载体干粉吸入剂制剂中的关键属性。
