title: Nebulization of active pharmaceutical ingredients with the eFlow(®) rapid: impact of formulation variables on aerodynamic characteristics.
abstract: Nebulization of active pharmaceutical ingredient (API) solutions is a well-established means to achieve pulmonary drug deposition. The current study identified the impact of formulation variables on the aerosolization performance of the eFlow(®) rapid with special respect to optimized lung application. API formulations (including excipient-supplemented samples) were investigated for physicochemical properties, then nebulized using vibrating-mesh technology. The generated aerosol clouds were analyzed by laser diffraction. Aerosol deposition characteristics in the human respiratory tract were estimated using an algebraic model. Remarkable effects on aerosolization performance [i.e., mass median aerodynamic diameter (MMAD)] of API solutions were obtained when the sample conductivity (by API concentration and type, sodium chloride addition) and dynamic viscosity (by application of sucrose and poly(ethylene glycol) 200) were elevated. A similar influence was observed for a decline in surface tension (by ethanol addition). Thus, a defined adjustment of formulation parameters allowed for a decrease of the MMAD from ∼ 8.0 μm to values as small as ∼ 3.5 μm. Consequently, the pattern and efficiency of aerosol deposition in the human respiratory tract were improved. In conclusion, identification of physicochemical variables and their way of influencing vibrating-mesh nebulization has been provided to deliver a platform for tailoring aerosol characteristics and thus, advancing pulmonary therapy.
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.forename: Nadine
authors.initials: N
authors.lastname: Prüfer
authors.forename: Nina
authors.initials: N
authors.lastname: Oesterheld
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
mesh_terms: D000336:Aerosols / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D008168:Lung / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013500:Surface Tension
chemical_list: D000336:Aerosols; D005079:Excipients; D011092:Polyethylene Glycols; D013395:Sucrose
keywords: active pharmaceutical ingredient; aerosol manipulation; aerosols; excipients; lung deposition; mass median aerodynamic diameter; particle size; preformulation; pulmonary drug delivery; vibrating-mesh nebulizer