Hybrid (BDBB) interferon-alpha: preformulation studies

A number of techniques, including RP-HPLC, HP-SEC and SDS-PAGE have been us ed 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 d egradation are via chemical transformation of the monomeric protein to a sp ecies 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 high er pH. The results have assisted in a targeted preformulation screen of pot entially stabilising excipients and possible parenteral solution dosage for ms have been identified. Preliminary 'real-time' storage data confirm excel lent chemical and physical stability of IFN-a in vehicles formulated at pH 7.6 or, especially, pH 4.0 under the proposed shelf conditions. (C) 1999 El sevier Science B.V. All rights reserved.