Formulation and physical characterization of large porous particles for inhalation.
OBJECTIVE
Relatively large (>5 microm) and porous (mass density <0.4 g/cm3) 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 inhalation or endogenous to the lungs; and second, to compare the aerodynamic 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), using a standard single-step spray-drying process. Aerosolization properties were assessed with a Spinhaler device in vitro in both an Andersen cascade impactor and an Aerosizer.


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 and 15 microm, and tap densities between 0.04 and 0.6 g/cm3. Theoretical estimates of mass mean aerodynamic diameter (MMAD) were rationalized and calculated in terms of geometric particle diameters and bulk tap densities. Experimental values of MMAD obtained from the Aerosizer most closely approximated the theoretical estimates, as compared to those obtained from the Andersen cascade impactor. Particles possessing high porosity and large size, with theoretical estimates of MMAD between 1-3 microm, exhibited emitted doses as high as 96% and respirable fractions ranging up to 49% or 92%, depending on measurement technique.


CONCLUSIONS
Dry powders engineered as large and light particles, and prepared with combinations of GRAS (generally recognized as safe) excipients, may be broadly applicable to inhalation therapy.
Vanbever
R
R
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
Mintzes
J D
JD
Wang
J
J
Nice
J
J
Chen
D
D
Batycky
R
R
Langer
R
R
Edwards
D A
DA
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003720:Densitometry; D005079:Excipients / Q000737:chemistry*; D066298:In Vitro Techniques; D008956:Models, Chemical; D010316:Particle Size; D016062:Porosity; D013501:Surface-Active Agents / Q000737:chemistry
D000336:Aerosols; D005079:Excipients; D013501:Surface-Active Agents