Article ; Online: Optimization of Particle Properties of Nanocrystalline Solid Dispersion Based Dry Powder for Inhalation of Voriconazole.
Journal of pharmaceutical sciences
2022 Volume 111, Issue 9, Page(s) 2592–2605
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Administration, Inhalation ; Aerosols/chemistry ; Dry Powder Inhalers/methods ; Humans ; Particle Size ; Powders/chemistry ; Silicon Dioxide ; Voriconazole |
| Chemical Substances | Aerosols ; Powders ; Silicon Dioxide (7631-86-9) ; Voriconazole (JFU09I87TR) |
| Language | English |
| Publishing date | 2022-06-11 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 3151-3 |
| ISSN | 1520-6017 ; 0022-3549 |
| ISSN (online) | 1520-6017 |
| ISSN | 0022-3549 |
| DOI | 10.1016/j.xphs.2022.06.007 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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