ABSTRACT
The development of parenteral solution dosage forms of interferon alpha 2 (rhIFN-alpha2) without human albumin may significantly diminish the problem of forming highly immunogenic rhIFN-alpha 2b aggregates and the potential risk of blood-transmitted diseases caused by infectious viruses and often living pathogens that may be present in the plasma. With this purpose, we evaluated the compatibility of type I borosilicate glass vials and chlorobutyl stoppers with rhIFN-alpha 2b in an aqueous solution. At the same time, we carried out a targeted formulation screen at 37 degrees C of single or combined (e.g. polysorbate 80, EDTA Na(2), PEG 400) potentially stabilizing excipients. Quantified biochemical results from 12 independent batches of rhIFN-alpha 2b in a polysorbate/benzyl alcohol-based vehicle formulated at pH 7.4 were all found within the limits established by the World Health Organization for this cytokine. Real-time storage data confirmed the excellent biochemical long-term (30 months) stability of rhIFN-alpha 2b in this aqueous solution formulation. Analyses were performed at intervals throughout the time period using reverse-phase high-performance liquid chromatography, a sandwich-type enzyme-linked immunosorbent assay, and antiviral activity as stability-indicating assays. Furthermore, both the physical stability (color, odor, appearance, pH, and absence of particulate material) and the sterility of this formulation were maintained under the proposed shelf conditions.
