Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
J Pharm Sci. 2010 Aug;99(8):3430-41. doi: 10.1002/jps.22101.
The relationship between physicochemical properties of drug/carrier blends and aerosol drug powder delivery was evaluated. Four pulmonary drugs each representing the major pulmonary therapeutic classes and with a different pharmacological action were employed. Specifically, the four pulmonary drugs were albuterol sulfate, ipratropium bromide monohydrate, disodium cromoglycate, and fluticasone propionate. The two carrier sugars, each representing a different sugar class, were D-mannitol and trehalose dihydrate. Dry powder aerosols (2%, w/w, drug in carrier) delivered using standardized entrainment tubes (SETs) were characterized by twin-stage liquid impinger. The fine particle fraction (FPF) was correlated with SET shear stress, tau(s), and the maximum fine particle fraction (FPF(max)) was correlated with a deaggregation constant, k(d), by using a powder aerosol deaggregation equation (PADE) by nonlinear and linear regression analyses applied to pharmaceutical inhalation aerosol systems in the solid state. For the four pulmonary drugs representing the major pulmonary therapeutic classes and two chemically distinct pulmonary sugar carriers (non-lactose types) aerosolized with SETs having well-defined shear stress values, excellent correlation and predictive relationships were demonstrated for the novel and rigorous application of PADE for dry powder inhalation aerosol dispersion within a well-defined shear stress range, in the context of pulmonary drug/sugar carrier physicochemical and interfacial properties.
评估了药物/载体混合物的物理化学性质与气溶胶药物粉末输送之间的关系。使用了四种代表主要肺部治疗类别且具有不同药理作用的肺部药物。具体而言，这四种肺部药物分别为硫酸沙丁胺醇、异丙托溴铵一水合物、二水合色甘酸钠和丙酸氟替卡松。两种载体糖，分别代表不同的糖类，为 D-甘露醇和海藻糖二水合物。使用标准化夹带管 (SET) 输送的干粉气溶胶 (2%，w/w，药物在载体中) 通过双级液体冲击器进行表征。通过使用粉末气溶胶解团聚方程 (PADE) 进行非线性和线性回归分析，将细颗粒分数 (FPF) 与 SET 剪切应力 τ(s) 相关联，将最大细颗粒分数 (FPF(max)) 与解团聚常数 k(d) 相关联，将其应用于固态下的制药吸入气溶胶系统。对于代表主要肺部治疗类别的四种肺部药物和两种具有明确定义剪切应力值的化学上不同的肺部糖载体（非乳糖类型），通过在肺部药物/糖载体物理化学和界面特性的背景下，在明确的剪切应力范围内，对于 PADE 在干粉吸入气溶胶分散中的新颖而严格的应用，展示了出色的相关性和预测关系。
