Long-term stabilization of recombinant human interferon alpha 2b in aqueous solution without serum albumin.
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.
Ruiz
Llamil
L
Formulation Development Department, Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, Havana, Cuba. ehardy@cigb.edu.cu
Reyes
Nuria
N
Duany
Ladys
L
Franco
Abrisleyda
A
Aroche
Kethia
K
Hardy Rando
Eugenio
E
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
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