Formulation and physical characterization of large porous particles for inhalation

Purpose. Relatively large (>5 mu m) and porous (mass density < 0.4 g/cm(3)) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for i nhalation or endogenous to the lungs; and second, to compare the aerodynami c size and performance of the particles with theoretical estimates based on bulk powder measurements. Methods. Dry powders were made of water-soluble excipients (e.g., lactose, albumin) combined with water-insoluble material (e.g., lung surfactant), us ing a standard single-step spray-drying process. Aerosolization properties were assessed with a Spinbaler(TM) device in vitro in both an Andersen casc ade impactor and an Aerosizer(TM). Results. By properly choosing excipient concentration and varying the spray drying parameters, a high degree of control was achieved over the physical properties of the dry powders. Mean geometric diameters ranged between 3 a nd 15 mu m, and tap densities between 0.04 and 0.6 g/cm(3). Theoretical est imates of mass mean aerodynamic diameter (MMAD) were rationalized and calcu lated in terms of geometric particle diameters and bulk tap densities. Expe rimental values of MMAD obtained from the Aerosizer(TM) most closely approx imated the theoretical estimates, as compared to those obtained from the An dersen cascade impactor. Particles possessing high porosity and large size, with theoretical estimates of MMAD between 1-3 mu m, exhibited emitted dos es as high as 96% and respirable fractions ranging up to 49% or 92%, depend ing on measurement technique.