Pulmonary delivery of peptide drugs: effect of particle size on bioavailability of leuprolide acetate in healthy male volunteers.

Leuprolide acetate, a nonapeptide with potent luteinizing hormone releasing hormone (LHRH) agonist activity, has low oral bioavailability. Unique aerosols of leuprolide acetate were developed and particle size distribution studies were carried out. A light scattering method (Malvern Model 2600c) was compared to the impaction method (Andersen Sampler) for measuring size distribution. Results showed the Malvern method to be comparable to the impaction method with the Malvern being faster and easier to use. Absolute bioavailability of leuprolide acetate in healthy human male volunteers ranged from 4% to 18% and agreed well with particle size data. Bioavailability corrected for respirable fraction ranged from 35% to 55%, indicating that the pulmonary route may have high potential for systemic delivery of this peptide.