Pharmaceutical formulation
AssigneeAstraZeneca UK Limited
InventorsPeng KE, Maria Gabriela BRUQUE, Katrina Jane DAY
Life of this patent
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Abstract
Described herein are stable pharmaceutical formulations for bioactive agents, including macromolecular bioactive agents such as polynucleotides and polypeptides. Also provided are medicaments and treatments using the pharmaceutical formulations described herein, as well as kits and methods of treating, preventing or managing a disease or disorder using the pharmaceutical formulations described herein.
Claims67
A stable pharmaceutical formulation comprising:
- (a) a bioactive agent;
- (b) a buffer;
- and
- (c) a surfactant comprising D-α-Tocopheryl polyethylene glycol succinate (TPGS),
- wherein the formulation has a pH from about 3 to about 9, about 4 to about 8 or about 5.5 to about 7.5.
The formulation of any of the preceding claims, wherein the concentration of TPGS is from about 0.001% to about 1%.
The formulation of any of the preceding claims, wherein the buffer is selected from acetate, acetic acid, succinate, succinic acid, phosphate, phosphoric acid, ascorbate, ascorbic acid, lactate, lactic acid, tartartic acid, maleic acid, glycine, gluconate, citrate, histidine, imidazole, bicarbonate and carbonic acid, sodium benzoate, benzoic acid, edetate, malate, tris, glycylglycine and mixtures thereof.
The formulation of the preceding claims, wherein the buffer has a concentration from about 0.1 mM to about 100 mM.
The formulation of any of the preceding claims, further comprising a tonicity agent.
The formulation of any of the preceding claims, further comprising an amino acid as an excipient.
The formulation of any of the preceding claims, further comprising a chelating agent.
A stable pharmaceutical formulation comprising:
- (a) from about 0.1 mg/mL to about 300 mg/mL bioactive agent;
- (b) from about 10 mM to about 50 mM buffer;
- (c) from about 0.01% to about 0.1% TPGS,
- wherein the formulation has a pH from about 3 to about 9.
The formulation of any of the preceding claims, comprising less than about 10,000, about about 1,000, about 750, about 500, about 250, about 150, about 100, or about 50 particles greater than about 2 μm, about 5 μm, about 10 μm, about 15 μm, about 20 μm or about 25 μm diameter/mL.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 40° C. for up to about 3 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 40° C. for up to about 6 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 25° C. for up to about 6 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 25° C. for up to about 12 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 2° C. to about 8° C. for up to about 12 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 2° C. to about 8° C. for up to about 24 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about 2° C. to about 8° C. for up to about 36 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −20° C. for up to about 6 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −20° C. for up to about 12 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −20° C. for up to 2 about 4 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −20° C. for up to about 36 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −80° C. for up to about 6 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −80° C. for up to about 12 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −80° C. for up to about 24 months.
The formulation of any of the preceding claims, wherein the formulation is stable at a temperature of about −80° C. for up to about 36 months.
A method of reducing particle formation in an aqueous pharmaceutical formulation, the method comprising adding D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) to the formulation, wherein less than about 10,000, about 5,000, about 1,000, about 750, about 500, about 250, about 150, about 100, or about 50 particles greater than about 2 μm, about 5 μm, about 10 μm, about 15 μm, about 20 μm or about 25 μm diameter/mL are formed.
A method of reducing interference during antibody-drug (ADC) conjugation comprising, adding D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) to a formulation comprising an unconjugated antibody intermediate.
Dependencies are inferred from the claim text.