Effect of dimethyl‐β‐cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in rats

The aim of this article is to prepare and characterize inhalable dry powders of recombinant human growth hormone (rhGH), and assess their efficacy for systemic delivery of the protein in rats. The powders were prepared by spray drying using dimethyl‐β‐cyclodextrin (DMβCD) at different molar ratios in the initial feeds. Size exclusive chromatography was performed in order to determine protecting effect of DMβCD on the rhGH aggregation during spray drying. By increasing the concentration of DMβCD, rhGH aggregation was decreased from 9.67 (in the absence of DMβCD) to 0.84% (using DMβCD at 1000 molar ratio in the spray solution). The aerosol performance of the spray dried (SD) powders was evaluated using Andersen cascade impactor. Fine particle fraction values of 53.49%, 33.40%, and 23.23% were obtained using DMβCD at 10, 100, and 1000 molar ratio, respectively. In vivo studies showed the absolute bioavailability of 25.38%, 76.52%, and 63.97% after intratracheal insufflation of the powders produced after spray drying of the solutions containing DMβCD at 10, 100, and 1000 molar ratio, respectively in rat. In conclusion, appropriate cyclodextrin concentration was achieved considering the protein aggregation and aerosol performance of the SD powders and the systemic absorption following administration through the rat lung. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5176-5185, 2008