Polysorbate mixtures having modified fatty acid ester distribution
The present disclosure provides polysorbate 20 compositions with particular fatty acid ester concentrations. In some embodiments, they may be used in pharmaceutical formulations, for example, to improve stability.
1 . A method of preparing a pharmaceutical formulation, the method comprising combining a drug and a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient comprises:
a polysorbate 20 composition comprising fatty acid esters, wherein the fatty acid esters of the polysorbate 20 composition comprise: 1.0% or less caproate, greater than or equal to 2.6% and less than or equal to 6.6% caprylate, greater than or equal to 2.4% and less than or equal to 6.4% caprate, greater than or equal to 55.0% and less than or equal to 60.0% laurate, greater than or equal to 14.1% and less than or equal to 18.1% myristate, greater than or equal to 7.0% and less than or equal to 10.9% palmitate, and less than or equal to 2.0% stearate;
wherein the drug is a protein, an antibody, an antibody fragment, an enzyme, or a peptide.
2 . The method of claim 1 , wherein the polysorbate 20 composition is from 0.01% to 0.12% (w/v) of the formulation.
3 . The method of claim 1 , wherein the concentration of drug is from 1% to 30% (w/v).
4 . The method of claim 1 , wherein the pH is from 4 to 8, or from 5 to 7.5, or from 6.5 to 7.5, or from 6.8 to 7.2.
5 . The method of claim 1 , wherein the pharmaceutically acceptable excipient further comprises water, an alcohol, a sugar, a buffer, a surfactant, a stabilizer, or combinations thereof.
6 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise greater than or equal to 3%, or greater than or equal to 3.5%, or greater than or equal to 4%, or greater than or equal to 4.6%, and less than or equal to 6.6% of caprylate.
7 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprises greater than or equal to 2.6%, or greater than or equal to 3%, or greater than or equal to 3.5%, or greater than or equal to 4%, or greater than or equal to 4.4%, and less than or equal to 6.4% caprate.
8 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise greater than or equal to 56%, greater than or equal to 57%, greater than or equal to 58% and less than or equal to 60% laurate.
9 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise greater than or equal to 14.1% and less than or equal to 18%, or less than or equal to 17%, or less than or equal to 16%, or less than or equal to 15% myristate.
10 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise greater than or equal to 7% and less than 10.9%, or less than or equal to 10%, or less than or equal to 9%, or less than or equal to 8% palmitate.
11 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise less than or equal to 2% or less than or equal to 1.5% or less than or equal to 1% stearate.
12 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise no detectable stearate.
13 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise 1% or less caproate, about 4.6% caprylate, about 4.8% caprate, about 57.0% laurate, about 16.2% myristate, about 9.4% palmitate, and no detectable stearate.
14 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise 1% or less caproate, from 3.7% to 5.2% caprylate, from 3.7% to 5.2% caprate, from 56.3% to 57.2% laurate, from 15.9% to 17.0% myristate, from 8.8% to 9.8% palmitate, and no detectable stearate.
15 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition comprise 1% or less caproate, from 3.5% to 5.5% caprylate, from 3.5% to 5.5% caprate, from 55% to 58% laurate, from 15% to 17.5% myristate, from 8.5% to 10% palmitate, and about 0.1% stearate or less.
16 . The method of claim 1 , wherein the fatty acid esters of the polysorbate 20 composition further comprises, greater than or equal to 5.8% and less than or equal to 9.8% oleate, and less than or equal to 2.0% linoleate.
17 . The method of claim 1 , wherein the drug is a protein.
18 . The method of claim 1 , wherein the drug is an antibody.
19 . The method of claim 1 , wherein the drug is a CHO-derived monoclonal antibody.
20 . The method of claim 1 , wherein the drug is a CHO-derived IgGb 1 monoclonal antibody.
21 . The method of claim 1 , wherein the drug is a CHO-derived IgG4 monoclonal antibody.