Journal of Pharmaceutical Sciences 2014-08-01

Nebulization of active pharmaceutical ingredients with the eFlow(®) rapid: impact of formulation variables on aerodynamic characteristics.

Moritz Beck-Broichsitter, Nadine Prüfer, Nina Oesterheld, Werner Seeger, Thomas Schmehl

文献索引：J. Pharm. Sci. 103(8) , 2585-9, (2014)

全文：HTML全文

摘要

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.© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.