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 (τs), using a novel powder aerosol deaggregation equation (PADE). Drug particles were < 5 μm in volume diameter with narrow unimodal distribution (Span < 1). The lowest shear SET (τs = 0.624 N/m2) gave a higher emitted dose (ED ~ 84-93%) and lower FPF (FPF6.4 ~ 7-25%). In contrast, the highest shear SET (τs = 13.143 N/m2) gave a lower ED (ED ~ 75-89%) and higher FPF (FPF6.4 ~ 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given τs, as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R2 ~ 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.