Research output: Contribution to journal › Article › peer-review
Large porous particles for respiratory drug delivery. Glycine-based formulations. / Ogienko, A. G.; Bogdanova, E. G.; Trofimov, N. A. et al.
In: European Journal of Pharmaceutical Sciences, Vol. 110, 15.12.2017, p. 148-156.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Large porous particles for respiratory drug delivery. Glycine-based formulations
AU - Ogienko, A. G.
AU - Bogdanova, E. G.
AU - Trofimov, N. A.
AU - Myz, S. A.
AU - Ogienko, A. A.
AU - Kolesov, B. A.
AU - Yunoshev, A. S.
AU - Zubikov, N. V.
AU - Manakov, A. Yu
AU - Boldyrev, V. V.
AU - Boldyreva, E. V.
N1 - Publisher Copyright: © 2017 Elsevier B.V.
PY - 2017/12/15
Y1 - 2017/12/15
N2 - Large porous particles are becoming increasingly popular as carriers for pulmonary drug delivery with both local and systemic applications. These particles have high geometric diameters (5–30 μm) but low bulk density (~ 0.1 g/cm3 or less) such that the aerodynamic diameter remains low (1–5 μm). In this study salbutamol and budesonide serve as model inhalable drugs with poor water solubility. A novel method is proposed for the production of dry powder inhaler formulations with enhanced aerosol performance (e.g. for salbutamol-glycine formulation the fine particle fraction (FPF ≤ 4.7 μm) value is 67.0 ± 1.3%) from substances that are poorly soluble in water. To overcome the problems related to extremely poor aqueous solubility of the APIs, not individual solvents are used for spray freeze-drying of API solutions, but organic-water mixtures, which can form clathrate hydrates at low temperatures and release APIs or their complexes as fine powders, which form large porous particles after the clathrates are removed by sublimation. Zwitterionic glycine has been used as an additive to API directly in solutions prior to spray freeze-drying, in order to prevent aggregation of powders, to enhance their dispersibility and improve air-flow properties. The clathrate-forming spray freeze-drying process in the multi-component system was optimized using low-temperature powder X-ray diffraction and thermal analysis.
AB - Large porous particles are becoming increasingly popular as carriers for pulmonary drug delivery with both local and systemic applications. These particles have high geometric diameters (5–30 μm) but low bulk density (~ 0.1 g/cm3 or less) such that the aerodynamic diameter remains low (1–5 μm). In this study salbutamol and budesonide serve as model inhalable drugs with poor water solubility. A novel method is proposed for the production of dry powder inhaler formulations with enhanced aerosol performance (e.g. for salbutamol-glycine formulation the fine particle fraction (FPF ≤ 4.7 μm) value is 67.0 ± 1.3%) from substances that are poorly soluble in water. To overcome the problems related to extremely poor aqueous solubility of the APIs, not individual solvents are used for spray freeze-drying of API solutions, but organic-water mixtures, which can form clathrate hydrates at low temperatures and release APIs or their complexes as fine powders, which form large porous particles after the clathrates are removed by sublimation. Zwitterionic glycine has been used as an additive to API directly in solutions prior to spray freeze-drying, in order to prevent aggregation of powders, to enhance their dispersibility and improve air-flow properties. The clathrate-forming spray freeze-drying process in the multi-component system was optimized using low-temperature powder X-ray diffraction and thermal analysis.
KW - Budesonide
KW - Clathrate hydrates
KW - Dry powder inhaler formulation
KW - Glycine
KW - Large porous particles
KW - Salbutamol
KW - Spray freeze-drying
KW - SYSTEM
KW - PERFORMANCE
KW - INHALATION
KW - BUDESONIDE
KW - IN-VITRO
KW - DRY POWDER INHALER
KW - WATER-SOLUBLE DRUGS
KW - X-RAY
KW - BETA-GLYCINE
KW - THERMODYNAMIC ASPECTS
KW - Humans
KW - Budesonide/chemistry
KW - Drug Carriers/chemistry
KW - Surface Properties
KW - Drug Compounding
KW - Dry Powder Inhalers
KW - Excipients
KW - Powders
KW - Freeze Drying
KW - Solubility
KW - Administration, Inhalation
KW - Glycine/chemistry
KW - Chemistry, Pharmaceutical
KW - Particle Size
KW - Albuterol/chemistry
KW - Drug Liberation
KW - Hydrophobic and Hydrophilic Interactions
KW - Porosity
KW - Aerosols/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85018931544&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2017.05.007
DO - 10.1016/j.ejps.2017.05.007
M3 - Article
C2 - 28479348
AN - SCOPUS:85018931544
VL - 110
SP - 148
EP - 156
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
ER -
ID: 9013881