PHARMACEUTICAL COMPOSITIONS OF TOFACITINIB FOR ORAL ADMINISTRATION
Liquid pharmaceutical compositions of tofacitinib or its pharmaceutically acceptable salts thereof are described, which are suitable for oral administration, and which are stable under varying storage conditions for extended periods of time. Methods of treating auto-immune disorders are also described, 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 comprising:
tofacitinib at a concentration of about 1 mg/mL;
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 a pH of the solution ranges from 3.5 to 5.0;
wherein the solution is free from precipitation when said solution is stored at 40° C./75% RH for 3 months; and
wherein said solution is a palatable oral solution.
2 . The solution according to claim 1 , wherein said solution further comprises one or more pharmaceutically acceptable excipients selected from stabilizers, solubilizers, pH adjusting agents, buffering agents, thickening agents, chelating agents, preservatives, flavoring agents, sweetening agents, coloring agents or mixtures thereof.
3 . The solution according to claim 1 , wherein the antioxidant is selected from 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, sodium metabisulfite or mixtures thereof.
4 . The solution according to claim 1 , wherein a 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 3 months.
5 . The solution according to claim 1 , wherein a level of Impurity B in the solution is less than 0.5% w/w as measured by HPLC, when said solution is stored at 40° C./75% RH for 3 months.
6 . 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.
7 . The solution according to claim 1 , wherein the anti-oxidant is present at a concentration of about 0.05% w/w of the solution.
8 . The solution according to claim 1 , wherein the antioxidant is tartaric acid.
9 . The solution according to claim 8 , wherein the tartaric acid is present in a concentration of about 0.05% w/w of the solution.
10 . The solution according to claim 8 , wherein the tartaric acid is present in a concentration of 0.5 mg/mL.
11 . The solution according to claim 1 , wherein the antioxidant is present, and wherein a weight ratio of the anti-oxidant to tofacitinib is from about 0.1:1 to about 1:10.
12 . The solution according to claim 1 , wherein tofacitinib is present at a concentration of about 1 mg/mL.
13 . The solution according to claim 12 , wherein tofacitinib at a concentration of about 1 mg/mL is provided as 1.62 mg/mL of tofacitinib citrate.