Constant size, variable density aerosol particles by ultrasonic spray freeze drying

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• 作者：Suzanne M. D&#8217 ; Addio^a ; ^b ; John Gar Yan Chan^a ; Philip Chi Lip Kwok^a ; Robert K. Prud&#8217 ; homme^b ; Hak-Kim Chan^a ; ^{kim.chan@sydney.edu.au}
• 关键词：da ; aerodynamic diameter ; dg ; geometric diameter ; 蟻 ; density ; dmode ; diameter corresponding to the mode of the particle size distribution ; BSA ; bovine serum albumin ; DPI ; dry powder inhaler ; FPF ; Fine Particle Fraction ; LN2 ; liquid nitrogen ; NGI ; Next Ge
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：10 May, 2012
• 卷：427
• 期：2
• 页码：185-191
• 文件大小：997 K

摘要

This work provides a new understanding of critical process parameters involved in the production of inhalation aerosol particles by ultrasonic spray freeze drying to enable precise control over particle size and aerodynamic properties. A series of highly porous mannitol, lysozyme, and bovine serum albumin (BSA) particles were produced, varying only the solute concentration in the liquid feed, c_s, from 1 to 5 wt%. The particle sizes of mannitol, BSA, and lysozyme powders were independent of solute concentration, and depend only on the drop size produced by atomization. Both mannitol and lysozyme formulations showed a linear relationship between the computed Fine Particle Fraction (FPF) and the square root of c_s, which is proportional to the particle density, 蟻, given a constant particle size d_g. The FPF decreased with increasing c_s from 57.0%to 16.6%for mannitol and 44.5%to 17.2%for lysozyme. Due to cohesion, the BSA powder FPF measured by cascade impaction was less than 10%and independent of c_s. Ultrasonic spray freeze drying enables separate control over particle size, d_g, and aerodynamic size, d_a which has allowed us to make the first experimental demonstration of the widely accepted rule d_a = d_g(蟻/蟻_o)^1/2 with particles of constant d_g, but variable density, 蟻 (蟻_o is unit density).