SPRAY-DRIED POWDERS AND POWDER BLENDS OF RECOMBINANT HUMAN DEOXYRIBONUCLEASE (RHDNASE) FOR AEROSOL DELIVERY

Purpose, We have used rhDNase to investigate the feasibility of develo ping a dry protein powder aerosol for inhalation delivery. Methods, Po wders of rhDNase alone and with sodium chloride were prepared by spray drying. Powder blends were obtained by mixing (tumbling and sieving) pure rhDNase powder with 'carrier' materials (lactose, mannitol or sod ium chloride). The weight percent of drug in the blends was between 5 and 70%. The particle size distributions and crystallinity of the spra y dried powders were obtained by laser diffraction and X-ray powder di ffraction, respectively. Particle morphology was examined by scanning electron microscopy. The ability of the powders and powder blends to b e dispersed into respirable aerosols was measured using a Rotahaler(TM ) connected to a multistage liquid impinger operating at 60 L/min. Res ults, Pure rhDNase powder was quite cohesive with a fine particle frac tion (FPF or 'respirable fraction': % wt. of particles < 7 mu m in the aerosol cloud) of about 20%. When particles also contained NaCl, the powders were dispersed better to form aerosols. A linear relationship was observed between the NaCl content and FPF for a similar primary si ze (similar to 3 mu m volume median diameter) of particles. The partic le morphology of these powders varied systematically with the salt con tent. For the blends, SEM revealed a monolayer-like adhesion of the fi ne drug particles to the carriers at drug contents greater than or equ al to 50 % wt. An overall 2-fold increase in FPF of rhDNase in the aer osol cloud was obtained for all the blends compared to the pure drug a erosols. Conclusions, The aerosol properties of spray dried rhDNase po wders can be controlled by incorporation of a suitable excipient, such as NaCl, and its relative proportion. Coarse carriers can also enhanc e the performance of rhDNase dry powder aerosols.