Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate.
The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (tau(s)), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 microm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (tau(s) = 0.624 N/m(2)) gave a higher emitted dose (ED approximately 84-93%) and lower FPF (FPF(6.4) approximately 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m(2)) gave a lower ED (ED approximately 75-89%) and higher FPF (FPF(6.4) approximately 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given tau(s), as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R(2) approximately 0.9804-0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction.
Xu
Zhen
Z
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Mansour
Heidi M
HM
Mulder
Tako
T
McLean
Richard
R
Langridge
John
J
Hickey
Anthony J
AJ
D000327:Adsorption; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000737:chemistry*; D003460:Crystallization; D004337:Drug Carriers; D004339:Drug Compounding / Q000295:instrumentation; D007785:Lactose / Q000737:chemistry*; D007834:Lasers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D013816:Thermodynamics; D014961:X-Ray Diffraction
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D004337:Drug Carriers; D011208:Powders; D007785:Lactose; D004205:Cromolyn Sodium; D000420:Albuterol