Pharmaceutical compositions of tofacitinib for oral administration
The present invention relates to liquid pharmaceutical compositions of tofacitinib or its pharmaceutically acceptable salts thereof, suitable for oral administration, that are stable under varying storage conditions for extended periods of time. The present invention also relates to methods of treating auto-immune disorders using the stable liquid pharmaceutical compositions of tofacitinib. A stable liquid pharmaceutical composition of tofacitinib according to the invention comprises of (a) tofacitinib at a concentration of about 1 mg/mL or more; (b) a pharmaceutically acceptable liquid vehicle; (c) at least one anti-oxidant; and (d) optionally one or more other pharmaceutically acceptable excipients.
1. A stable solution of tofacitinib consisting essentially of:
tofacitinib at a concentration of about 1 mg/mL, and optionally one or more antioxidants; and
a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof;
wherein pH of the solution ranges from 3.7 to 4.5;
wherein the solution is free from precipitation when said solution is stored at 25° C./60% RH for at least 6 months;
wherein level of total impurities in the solution is less than 1.5% w/w as measured by HPLC, when said solution is stored at 40° C./75% RH for 6 months;
wherein said solution is a palatable oral solution.
2. The solution according to claim 1 , said solution further comprising one or more other pharmaceutically acceptable excipients selected from the group consisting of stabilizers, solubilizers, pH adjusting agents, buffering agents, thickening agents, chelating agents, preservatives, flavoring agents, sweetening agents, coloring agents and mixtures thereof.
3. The solution according to claim 1 , wherein the anti-oxidant is selected from the group consisting of sodium bisulfate, ascorbic acid, ascorbyl palmitate, citric acid, tartaric acid, glycine, L-cysteine hydrochloride, L-methionine, butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), hydro phosphorous acid, monothioglycerol, propyl gallate, sodium ascorbate, sodium citrate anhydrous, sodium citrate dihydrate, sodium sulfide, sodium sulfite, sodium bisulfite, sodium formaldehyde sulfoxylate, thioglycolic acid and sodium metabisulfite.
4. The solution according to claim 1 , wherein the concentration of the anti-oxidant ranges from about 0.01% to about 50% w/w of the solution.
5. The solution according to claim 1 , wherein the anti-oxidant is present at a concentration of about 0.05% w/w of the solution.
6. The solution according to claim 1 , wherein the anti-oxidant is tartaric acid.
7. The solution according to claim 6 , wherein the tartaric acid is present in the concentration of about 0.05% w/w of the solution.
8. The solution according to claim 6 , wherein the tartaric acid is present in an amount of 0.5 mg/mL.
9. The solution according to claim 1 , wherein the weight ratio of the anti-oxidant to tofacitinib is from about 0.1:1 to about 1:10.
10. A stable solution of tofacitinib consisting essentially of: tofacitinib at a concentration of about 1 mg/mL, and optionally one or more antioxidants;
a pharmaceutically acceptable liquid vehicle selected from the group consisting of water, purified water, ethanol or a combination thereof;
wherein pH of the solution ranges from 3.7 to 4.5;
wherein the solution is free from precipitation when said solution is stored at 25° C./60% RH for at least 6 months;
wherein level of total impurities in the solution is less than 1.5% w/w as measured by HPLC, when said solution is stored at 40° C./75% RH for 6 months;
wherein said solution is a palatable oral solution and wherein said oral solution further comprises one or more other pharmaceutically acceptable excipients selected from the group consisting of stabilizers, solubilizers, pH adjusting agents, buffering agents, thickening agents, chelating agents, preservatives, flavoring agents, sweetening agents, coloring agents and mixtures thereof.