Dry powder aerosols generated by standardized entrainment tubes from alternative sugar blends: 3. Trehalose dihydrate and D-mannitol carriers.
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.
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
Heidi M
HM
Mansour
Zhen
Z
Xu
Anthony J
AJ
Hickey
D000336:Aerosols; D000465:Algorithms; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004055:Differential Thermal Analysis; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D009241:Ipratropium; D007834:Lasers; D008353:Mannitol / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D014199:Trehalose / Q000737:chemistry*
D000336:Aerosols; D001993:Bronchodilator Agents; D002241:Carbohydrates; D004337:Drug Carriers; D008353:Mannitol; D014199:Trehalose; D009241:Ipratropium