Stability of Nonaqueous Suspension Formulations of Plasma Derived Factor IX and Recombinant Human Alpha Interferon at Elevated Temperatures.

Purpose. To identify a suitable nonaqueous, parenterally acceptable suspending vehicle whereby a therapeutic protein is delivered as a stable flowable powder, making it amenable to delivery from sustained delivery systems maintained at body temperature. Methods. Formulations of plasma derived Factor IX (pdFIX) and recombinant human alpha interferon (rhα-lFN) were formulated as dry powders, suspended in various vehicles (perfluorodecalin, perfluorotributylamine, methoxyflurane, polyethylene glycol 400, soybean oil, tetradecane or octanol) and stored at 37°C. Stability was assessed by size exclusion chromatography, reverse phase chromatography, ion exchange chromatography, and bioassay, and was compared to the stability of dry powder formulations stored at 37°C and −80°C. Results. PdFIX was stable when stored at 37°C as a dry powder, or when the dry powder was suspended in the pharmaceutically acceptable vehicles perfluorodecalin or perfluorotributylamine. Suspensions of the powder in other pharmaceutically/parenterally acceptable vehicles such as soybean oil or PEG 400 resulted in aggregation and loss of bioactivity. A dry powder formulation of rhα-lFN suspended in perfluorodecalin was also stable at 37°C. Conclusions. This study shows the potential utility of perfluorinated hydrocarbons as nonaqueous suspending vehicles for long term in-vivo delivery of therapeutic proteins. [ABSTRACT FROM AUTHOR]