Engstrom Josh D, Tam Jasmine M, Miller Maria A, Williams Robert O, Johnston Keith P
Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.
Pharm Res. 2009 Jan;26(1):101-17. doi: 10.1007/s11095-008-9707-z. Epub 2008 Aug 29.
A novel concept is presented for the formation of stable suspensions composed of low density flocs of high aspect ratio drug particles in hydrofluoroalkane (HFA) propellants, and for subdividing (templating) the flocs with aerosolized HFA droplets to achieve high fine particle fractions with a pressurized metered dose inhaler.
Bovine serum albumin (BSA) nanorods, produced by thin film freezing (TFF), were added to HFA to form a suspension. Particle properties were analyzed with an Anderson cascade impactor (ACI), static and dynamic light scattering and optical microscopy.
The space filling flocs in HFA were stable against settling for one year. The pMDI produced high fine particle fractions (38-47%) with an emitted dose of 0.7 mg/actuation. The atomized HFA droplets break apart, that is template, the highly open flocs. Upon evaporation of HFA, capillary forces shrink the templated flocs to produce porous particles with optimal aerodynamic diameters for deep lung delivery.
Open flocs composed of nanorods, stable against settling, may be templated during actuation with a pMDI to produce optimal aerodynamic diameters and high fine particle fractions. This concept is applicable to a wide variety of drugs without the need for surfactants or cosolvents to stabilize the primary particles.
提出了一种新的概念，用于在氢氟烷烃（HFA）推进剂中形成由高纵横比药物颗粒的低密度絮凝物组成的稳定悬浮液，并通过雾化的HFA液滴对絮凝物进行细分（模板化），以通过定量压力吸入器实现高细颗粒分数。
将通过薄膜冷冻（TFF）制备的牛血清白蛋白（BSA）纳米棒添加到HFA中以形成悬浮液。使用安德森级联撞击器（ACI）、静态和动态光散射以及光学显微镜分析颗粒性质。
HFA中的空间填充絮凝物在一年内沉降稳定。定量压力吸入器产生了高细颗粒分数（38-47%），每次喷射剂量为0.7毫克。雾化的HFA液滴会分裂，即模板化高度开放的絮凝物。HFA蒸发后，毛细管力使模板化的絮凝物收缩，以产生具有适合深部肺部给药的最佳空气动力学直径的多孔颗粒。
由纳米棒组成的开放絮凝物，沉降稳定，在使用定量压力吸入器启动过程中可进行模板化，以产生最佳空气动力学直径和高细颗粒分数。这一概念适用于多种药物，无需表面活性剂或助溶剂来稳定初级颗粒。
