title: Long-term stabilization of recombinant human interferon alpha 2b in aqueous solution without serum albumin.
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.
authors.affiliation: Formulation Development Department, Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, Havana, Cuba. ehardy@cigb.edu.cu
authors.forename: Llamil
authors.initials: L
authors.lastname: Ruiz
authors.forename: Nuria
authors.initials: N
authors.lastname: Reyes
authors.forename: Ladys
authors.initials: L
authors.lastname: Duany
authors.forename: Abrisleyda
authors.initials: A
authors.lastname: Franco
authors.forename: Kethia
authors.initials: K
authors.lastname: Aroche
authors.forename: Eugenio
authors.initials: E
authors.lastname: Hardy Rando
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients; D005898:Glass; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D007263:Infusions, Parenteral; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D011994:Recombinant Proteins; D012709:Serum Albumin; D013997:Time Factors; D014867:Water
chemical_list: D000998:Antiviral Agents; D005079:Excipients; D006845:Hydrocarbons, Fluorinated; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019999:Pharmaceutical Solutions; D011994:Recombinant Proteins; D012709:Serum Albumin; D014867:Water