Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 2. Ipratropium bromide monohydrate and fluticasone propionate.
The objectives of this study were: systematic investigation of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs; mechanistic evaluation of performance data by powder aerosol deaggregation equation (PADE). The drugs (IPB and FP) were prepared in sieved and milled lactose carriers (2% w/w). Aerosol studies were performed using SETs (shear stresses tau(s) = 0.624-13.143 N/m(2)) by twin-stage liquid impinger, operated at 60 L/min. PADE was applied for formulation screening. Excellent correlation was observed when PADE was adopted correlating FPF to tau(s). Higher tau(s) corresponded to higher FPF values followed by a plateau representing invariance of FPF with increasing tau(s). The R(2) values for PADE linear regression were 0.9905-0.9999. Performance described in terms of the maximum FPF (FPF(max): 15.0-37.6%) resulted in a rank order of ML-B/IPB > ML-A/IPB > SV-A/IPB > SV-B/IPB > ML-B/FP > ML-A/FP > SV-B/FP > SV-A/FP. The performance of IPB was superior to FP in all formulations. The difference in lactose monohydrate carriers was less pronounced for the FPF in IPB than in FP formulations. The novel PADE offers a robust method for evaluating aerodynamic performance of dry powder formulations within a defined tau(s) range.
Xu
Zhen
Z
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
Mansour
Heidi M
HM
Mulder
Tako
T
McLean
Richard
R
Langridge
John
J
Hickey
Anthony J
AJ
D000280:Administration, Inhalation; D000336:Aerosols; D000465:Algorithms; D000730:Androstadienes / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D000068298:Fluticasone; D009241:Ipratropium / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D007834:Lasers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D014961:X-Ray Diffraction
D000336:Aerosols; D000730:Androstadienes; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D000068298:Fluticasone; D009241:Ipratropium; D007785:Lactose