Shetty Nivedita, Hau Jonathan, Yanez Evelyn, Shur Jag, Cheng Joan, Sun Changquan Calvin, Nagapudi Karthik, Narang Ajit
Departments of Small Molecule Pharmaceutical Sciences, Genentech, Inc., One DNA Way, South San Francisco, CA 94080, USA.
Nanopharm Ltd, an Aptar Pharma Company, Cavendish House, Hazell Drive, Newport NP10 8FY, U.K.
J Pharm Sci. 2022 Apr;111(4):1152-1163. doi: 10.1016/j.xphs.2021.09.004. Epub 2021 Sep 8.
High drug load inhalable particles were prepared by co-spray drying a hydrophobic, crystalline, small molecule drug with various lipid or phospholipid excipients at a 9:1 molar ratio to understand the primary drivers of aerosol performance. The effect of excipient structure on solid-state, surface characteristics, and aerodynamic performance of the co-spray dried particles was studied while keeping the spray drying parameters constant. Spray drying of the drug with lipids produced crystalline drug particles, whereas phospholipids produced partially amorphous drug particles. All of the co-spray dried particles were nearly spherical with a smooth surface, except for the spray dried drug particles without excipients - which showed the presence of rough crystals on the surface. All co-spray dried particles showed surface enrichment of the excipient. The surface enrichment of the phospholipids was higher compared to the lipids. Co-spray dried particles that showed higher surface enrichment of excipients showed improved aerosol performance. In comparing all the excipients studied, distearyolphosphatidylcholine (DSPC) showed maximum enrichment on the particle surface and thereby significantly improved aerosol performance. This study demonstrated that the addition of small amounts of lipid excipients during spray drying can change surface morphology, composition, and cohesion, impacting aerosol performance of drugs.
通过将疏水性结晶小分子药物与各种脂质或磷脂辅料以9:1的摩尔比进行共喷雾干燥，制备了高载药量可吸入颗粒，以了解气雾剂性能的主要驱动因素。在保持喷雾干燥参数不变的情况下，研究了辅料结构对共喷雾干燥颗粒的固态、表面特性和空气动力学性能的影响。药物与脂质共喷雾干燥产生结晶药物颗粒，而与磷脂共喷雾干燥产生部分无定形药物颗粒。除了没有辅料的喷雾干燥药物颗粒表面存在粗糙晶体外，所有共喷雾干燥颗粒几乎都是表面光滑的球形。所有共喷雾干燥颗粒都表现出辅料在表面的富集。与脂质相比，磷脂的表面富集程度更高。辅料表面富集程度较高的共喷雾干燥颗粒表现出气雾剂性能的改善。在比较所有研究的辅料时，二硬脂酰磷脂酰胆碱（DSPC）在颗粒表面表现出最大程度的富集，从而显著改善了气雾剂性能。这项研究表明，喷雾干燥过程中添加少量脂质辅料可以改变表面形态、组成和内聚力，从而影响药物的气雾剂性能。
