title: Stability of Ala 125 recombinant human interleukin-2 in solution.
abstract: Herein, we describe the preformulation study of Ala 125- recombinant human interleukin-2 (rhIL-2A(125)) in solution. This modified form of the natural human IL-2 is obtained by the replacement of cysteine with alanine at position 125. The compatibility of this rhIL-2A(125) with type I borosilicate glass vials showed no significant adsorption at liquid-vial interface. The effect of single excipients on the stability of this lymphokine was evaluated through RP-HPLC, SDS-PAGE and biological activity assay. Polysorbate 80 at high concentrations decreased the stability of rhIL-2A(125) in solution. On the other hand, the use of antioxidants (methionine and EDTA Na(2)) diminished the oxidation rate of the active ingredient. Additionally, a group of amino acids (glutamine, alanine, glycine and histidine) stabilized rhIL-2A(125) in different grades, and glycine at 5 mg mL(-1) allowed for the best stability behaviour. Taken together, these preformulation results can be used to design an adequate liquid vehicle for rhIL-2A(125) to be manufactured for human use.
authors.affiliation: Center for Genetic Engineering and Biotechnology, P. O. Box 6162, Havana, Cuba.
authors.forename: Nuria
authors.initials: N
authors.lastname: Reyes
authors.forename: Llamil
authors.initials: L
authors.lastname: Ruiz
authors.forename: Kethia
authors.initials: K
authors.lastname: Aroche
authors.forename: Haydee
authors.initials: H
authors.lastname: Gerónimo
authors.forename: Olga
authors.initials: O
authors.lastname: Brito
authors.forename: Eugenio
authors.initials: E
authors.lastname: Hardy
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004349:Drug Packaging; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005079:Excipients; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D019999:Pharmaceutical Solutions; D011136:Polysorbates; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D005079:Excipients; D007376:Interleukin-2; D019999:Pharmaceutical Solutions; D011136:Polysorbates; D011994:Recombinant Proteins