SOLID-STATE CHARACTERIZATION OF SPRAY-DRIED POWDERS OF RECOMBINANT HUMAN DEOXYRIBONUCLEASE (RHDNASE)

rhDNase is a recombinant human protein approved as an aqueous solution for human use by inhalation. To study the feasibility of preparation of dry powders for inhalation, spray-dried powders of pure rhDNase and co-spray-dried mixtures of rhDNase with an excipient approved for inh alation products, lactose, were prepared. Both types of powders were i nitially amorphous. The lactose, however, was found to crystallize aft er exposure to a humid environment. The crystals in the powder were id entified as the alpha-monohydrate polymorph of lactose by hot-stage op tical and scanning electron microscopy, differential scanning calorime try and thermogravimetry, FTIR spectroscopy, and X-ray powder diffract ion. Moisture sorption isotherms indicated that crystallization occurr ed at high relative humidities (70-85%), depending on the temperature of the environment (5-40 degrees C). The practical implications for th e manufacturing and storage of protein powders for inhalation are disc ussed.