Stable, Benzyl Alcohol-free Aqueous Solution Formulations Containing Alpha-type Interferon
AssigneeHoffmann-La Roche Inc.
InventorsUlla Grauschopf, Michael Adler, Hanns-Christian Mahler, Felix Heise, Susanne Baroth
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Abstract
The present invention provides a stable, isotonic, aqueous solution formulation comprising: (i) 0.1-0.5 mg/mL alpha-type interferon, preferably pegylated alpha-type interferon; (ii) 20 mM Acetate buffer system to maintain a pH of 6.0±0.5; (iii) 5-20 mM L-methionine; (iv) 120-150 mM sodium chloride; (v) 0.01-0.07 percent by weight of a surfactant effective to stabilize the alpha-type interferon, preferably pegylated alpha-type interferon against loss of its activity and (vi) an amount of water for injection sufficient to prepare a solution of the above-listed ingredients.
Claims11
A stable, isotonic, aqueous solution formulation comprising:
- (i) 0.1-0.5 mg/mL alpha-type interferon, preferably pegylated alpha-type interferon;
- (ii) 20 mM Acetate buffer system to maintain a pH of 6.0±0.5;
- (iii) 5-20 mM L-methionine;
- (iv) 120-150 mM sodium chloride;
- (v) 0.01-0.07 percent by weight of a surfactant effective to stabilize the alpha-type interferon, preferably pegylated alpha-type interferon against loss of its activity and
- (vi) an amount of water for injection sufficient to prepare a solution of the above-listed ingredients.
A stable aqueous solution formulation comprising:
- (i) Pegylated alpha-type interferon of formula (I)
- wherein R and R′ are methyl, X is NH, the average sum of n and n′ is 850 to 1000, the molecular weight of the polyethylene glycol units is about 40 kDa and the interferon alpha is an interferon alpha-2a;
- (ii) acetate buffer to maintain a pH of 6.0±0.5;
- (iii) L-methionine;
- (iv) sodium chloride;
- (v) Polysorbate 20;
- and,
- (vi) water for injection.
A stable aqueous solution formulation comprising:
- (i) Pegylated alpha-type interferon of formula (I)
- wherein R and R′ are methyl, X is NH, the average sum of n and n′ is 850 to 1000, the molecular weight of the polyethylene glycol units is about 40 kDa and the interferon alpha is an interferon alpha-2a;
- (ii) acetate buffer to maintain a pH of 6.0±0.5;
- (iii) L-methionine;
- (iv) sodium chloride;
- (v) poloxamer 188;
- and,
- (vi) water for injection.
A method for preparing a stable, isotonic, aqueous solution formulation comprising high biological alpha-type interferon activity, preferably pegylated alpha-type interferon activity, comprising admixing:
- (i) 0.1-0.5 mg/mL alpha-type interferon, preferably pegylated alpha-type interferon;
- (ii) 20 mM Acetate buffer system to maintain a pH of 6.0±0.5;
- (iii) 10 mM L-methionine;
- (iv) 140 mM sodium chloride;
- (v) 0.02 percent by weight of a surfactant effective to stabilize the alpha-type interferon, preferably pegylated alpha-type interferon against loss of its activity;
- and,
- (vi) sufficient amount of water to make an aqueous solution.
Dependencies are inferred from the claim text.