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 mu m 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 similar to 84-93%) and lower FPF (FPF(6.4) similar to 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m2) gave a lower ED (ED 75-89%) and higher FPF (FPF(6 4) similar to 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) similar to 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. (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3398-3414, 2010