Heterogeneous Particle Deaggregation and Its Implication for Therapeutic Aerosol Performance

Abstract

Aerosolization performance of dry powder blends of drugs for the treatment of asthma or chronic obstructive pulmonary diseases have been reported in three previous articles In vitro aerosolization was performed at defined shear stresses (0.624-13 143 N/m(2)). Formulations were characterized aerodynamically and powder aerosol deaggregation equations (PADE) and corresponding linear regression analyses for pharmaceutical aerosolization were applied Particle deaggregation is the result of overcoming fundamental forces acting at the particle interface. A new method, PADE, describing dry powder formulation performance in a shear stress range has been developed which may allow a fundamental understanding of interparticulate and surface forces The application of FADE predicts performance efficiency and reproducibility and supports rational design of dry powder formulations. The analogy of aerosol performance with surface molecular adsorption has important implications. Expressions describing surface adsorption were intended to allow elucidation of mechanisms involving surface heterogeneity, lateral interaction, and multilayer adsorption of a variety of materials By using a similar expression for drug aerosolization performance, it is conceivable that an analogous mechanistic approach to the evaluation of particulate systems would be possible., (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3442-3461, 2010