Hollow porous particles in metered dose inhalers

Purpose. To assess the physical stability and aerosol characteristics of su spensions of hollow porous microspheres (PulmoSpheres(TM)) in HFA-134a. Methods. Cromolyn sodium, albuterol sulfate, and formoterol fumarate micros pheres were prepared by a spray-drying method. Particle size and morphology were determined via electron microscopy. Particle aggregation and suspensi on creaming times were assessed visually, and aerosol performance was deter mined via Andersen cascade impaction and dose uniformity studies. Results. The hollow porous particle morphology allows the propellant to per meate freely within the particles creating a novel form of suspension terme d a homodispersion(TM), wherein the dispersed and continuous phases ate ide ntical, separated by an insoluble interfacial layer of drug and excipient. Homodispersion formation improves suspension stability by minimizing the di fference in density between the particles and the medium, and by reducing a ttractive forces between particles. The improved physical stability leads t o excellent dose uniformity. Excellent aerosolization efficiencies are also observed with PulmoSpheres formulations, with fine particle fractions of a bout 70%. Conclusions. The formation of hollow porous particles provides a new formul ation technology for stabilizing suspensions of drugs in hydrofluoroalkane propellants with improved physical stability, content uniformity, and aeros olization efficiency.