Hollow porous particles in metered dose inhalers.

Abstract

Purpose. To assess the physical stability and aerosol characteristicsof suspensions of hollow porous microspheres (PulmoSpheres™) inHFA-134a. Methods. Cromolyn sodium, albuterol sulfate, and formoterol fumaratemicrospheres were prepared by a spray-drying method. Particle sizeand morphology were determined via electron microscopy. Particleaggregation and suspension creaming times were assessed visually,and aerosol performance was determined via Andersen cascadeimpaction and dose uniformity studies. Results. The hollow porous particle morphology allows the propellantto permeate freely within the particles creating a novel form ofsuspension termed a homodispersion™, wherein the dispersed and continuousphases are identical, separated by an insoluble interfacial layer of drugand excipient. Homodispersion formation improves suspension stabilityby minimizing the difference in density between the particles andthe medium, and by reducing attractive forces between particles. Theimproved physical stability leads to excellent dose uniformity. Excellentaerosolization efficiencies are also observed with PulmoSpheresformulations, with fine particle fractions of about 70%. Conclusions. The formation of hollow porous particles provides anew formulation technology for stabilizing suspensions of drugs inhydrofluoroalkane propellants with improved physical stability, contentuniformity, and aerosolization efficiency.