title: Hybrid (BDBB) interferon-alpha: preformulation studies.
abstract: A number of techniques, including RP-HPLC, HP-SEC and SDS-PAGE have been used in the delineation of degradative mechanisms of recombinant hybrid (BDBB) interferon-alpha (IFN-alpha) in the solution phase. Different degradation profiles are found according to medium pH. At pH 4.0 the major routes of degradation are via chemical transformation of the monomeric protein to a species which retains antiviral activity, and by self-proteolytic hydrolysis. At pH 7.6, methionine-oxidation is the major chemical degradative process. Protein aggregation is also a significant route of degradation at the higher pH. The results have assisted in a targeted preformulation screen of potentially stabilising excipients and possible parenteral solution dosage forms have been identified. Preliminary 'real-time' storage data confirm excellent chemical and physical stability of IFN-alpha in vehicles formulated at pH 7.6 or, especially, pH 4.0 under the proposed shelf conditions.
authors.affiliation: Drug Preformulation and Delivery Department, Ciba Pharmaceuticals (now Novartis Horsham Research Centre), Wimblehurst Road, Horsham, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Bentley
authors.forename: R A
authors.initials: RA
authors.lastname: Stringer
authors.forename: N
authors.initials: N
authors.lastname: Lowther
mesh_terms: D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004492:Edetic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D016898:Interferon-alpha / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D012996:Solutions
chemical_list: D016898:Interferon-alpha; D011994:Recombinant Proteins; D012996:Solutions; D004492:Edetic Acid