Design And Evaluation Of Dry Powder For Inhalation Of Recombinant Human Interferon α-2b

Recombinant human interferon alpha-2b (IFNα-2b), an endogenous cytokine, possesses antivirus, antiproliferation and immunomodulation properties. In this article, aerosol dry powder form of the protein was investigated as an alternate administration route to traditional injections. The comprehensive studies on IFNα-2b dry powder for inhalation was performed based on the protein stability, dispersibility of the dry powder and the pharmacokinetic and pharmacodynamic behavior. Five main sections were included in this paper:1 , The study on the absorption through the pulmonary route using rabbit as experimental animal:IFNα-2b was administrated by intravenous, subcutaneous (s.c.) and intratracheal (i.t.) administration, and sodium tauroglycocholate and citric acid were used as absorption promoters in i.t. rabbits. The data from these studies revealed that the relative pulmonary bioavailability of IFNα-2b was much lower than 1% with no promoters, compared to s.c. administration. The serum concentration increased by about 30-50 times with the absorption promoters. Despite the limits of our study and the poor bioavailability we were able to demonstrate the feasibility of no-invasive delivery of IFNα-2b.2, Investigation into the stability of IFNα-2b in the rotary vacuum evaporation process and spray drying process:(1) Effects of buffer system, pH, temperature and additives on the stability of IFNα-2b during the rotary vacuum evaporation were investigated. Citric acid-Na₂HPO₄ buffer system (pH 7.0) was necessary to maintain activity. A number of additives were tested for their protective effects, among which carbopol 934, HPMC (20000cp), lysine, methionine, povidone(K30), MgSO₄, lecithin, PEG-6000, polysorbate 20/80, polyvinyl alcohol, Hydroxypropyl-beta-cyclodextrin (HP-β-CD), sodium dodecylbenzene sulfonate (SDS) were proved to be powerful in decreasing the activity loss.(2) Effects of atomization air flow, inlet air temperature and additives on the stability of IFN-α2b during spray drying were studied. Either low atomization air flow or low inlet air...