Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar, Mohali, Punjab, 160062, India.
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar, Mohali, Punjab, 160062, India.
J Pharm Sci. 2022 Sep;111(9):2592-2605. doi: 10.1016/j.xphs.2022.06.007. Epub 2022 Jun 11.
A one-step spray drying based process was employed to generate ready-to-use nanocrystalline solid dispersion (NCSD) dry powder for inhalation (DPI) of voriconazole (VRC). The solid dispersion was prepared by spray drying VRC, MAN (mannitol) and soya lecithin (LEC) from mixture of methanol-water. Various formulation and process related parameters were screened, including LEC, inlet temperature, total solid content and feed flow rate to generate particles of geometric size ≤5 µm. Aerosil® 200 was explored as the quaternary excipient either during spray drying or by physically mixing with the optimized ternary NCSD. The powders were extensively characterized for solid form, primary particle size, assay, embedded nanocrystal size, morphology, porosity, density and moisture content. Aerodynamic properties were studied using next generation impactor (NGI), while surface elemental composition and topography were investigated using SEM-EDS (scanning electron microscopy- energy dispersive spectroscopy) and AFM (atomic force microscopy), respectively. At selected inlet temperature of 120 ˚C, total solid content and feed flow rate significantly impacted the size of primary NCSD particles. Size of primary particles increased with increase in total solid content and feed flow rate of the solution. VRC nanocrystals were obtained in polymorphic Form B whereas the matrix of MAN consisted of mixture of polymorphic Forms α, β and δ. SEM-EDS analysis confirmed deposition of Aerosil® 200 on surface of spray dried particles. In addition to increased porosity and reduced density, increase in surface roughness of particles (evident from AFM topographic analysis) contributed to enhanced powder deposition at stages 3 and 4 in NGI. In comparison, physical blending of NCSD with Aerosil® 200 showed improvement in aerosolization due to flow enhancement property.
采用一步喷雾干燥法制备了伏立康唑（VRC）的即用型纳米晶固体分散体（NCSD）干粉吸入剂（DPI）。将 VRC、MAN（甘露醇）和大豆卵磷脂（LEC）从甲醇-水混合物中喷雾干燥，制备固体分散体。筛选了各种制剂和工艺相关参数，包括 LEC、进口温度、总固体含量和进料流速，以生成几何尺寸≤5μm 的颗粒。Aerosil®200 被探索作为季铵赋形剂，无论是在喷雾干燥过程中还是与优化的三元 NCSD 物理混合时。粉末的固体形式、初级粒径、含量、嵌入纳米晶尺寸、形态、孔隙率、密度和水分含量都进行了广泛的表征。使用下一代撞击器（NGI）研究了空气动力学特性，而使用扫描电子显微镜-能量色散光谱（SEM-EDS）和原子力显微镜（AFM）研究了表面元素组成和形貌。在选定的进口温度 120°C 下，总固体含量和进料流速显著影响初级 NCSD 颗粒的尺寸。初级颗粒的尺寸随总固体含量和溶液的进料流速的增加而增加。VRC 纳米晶体以多晶型 B 获得，而 MAN 的基质由多晶型 α、β和 δ的混合物组成。SEM-EDS 分析证实 Aerosil®200 沉积在喷雾干燥颗粒的表面上。除了增加孔隙率和降低密度外，颗粒表面粗糙度的增加（从 AFM 形貌分析中明显看出）有助于在 NGI 的第 3 阶段和第 4 阶段增强粉末沉积。相比之下，NCSD 与 Aerosil®200 的物理混合由于增强了流动性能而改善了空气悬浮。
