STABLE PHARMACEUTICAL COMPOSITIONS OF HYDROXYUREA
The present invention relates to oral pharmaceutical compositions comprising: (i) hydroxyurea at a concentration of about 10 mg/mL to about 100 mg/mL; (ii) at least one pharmaceutically acceptable liquid vehicle; (iii) one or more amino acids at a concentration of about 0.1 mg/mL to 10.0 mg/mL, and (iv) 0.001% to 10% of one or more pharmaceutically acceptable excipients, wherein the composition is in the form of a ready-to-use and safe-to-administer solution suitable for oral administration, wherein the hydroxyurea is dissolved in the liquid vehicle and the solution is homogeneous, and wherein the solution is stable, such that the level of carbamoyloxyurea in the solution is less than 0.5% w/w as measured by HPLC upon storage at 25° C./60% RH for at least 3 months, or at 2-8° C. for at least 12 months.
1 . A pharmaceutical composition comprising:
(i) hydroxyurea at a concentration of about 10 mg/mL to about 100 mg/ml;
(ii) at least one pharmaceutically acceptable liquid vehicle;
(iii) one or more amino acids at a concentration of about 0.1 mg/mL to 10.0 mg/mL, and
(iv) 0.001% to 10% of one or more pharmaceutically acceptable excipients,
wherein the composition is in the form of a ready-to-use and safe-to-administer solution suitable for oral administration,
wherein the hydroxyurea is dissolved in the liquid vehicle and the solution is homogeneous, and
wherein the solution is stable, such that the level of carbamoyloxyurea in the solution is less than 0.5% w/w as measured by HPLC, when the solution is stored at 25° C./60% RH for at least 3 months.
2 . The composition according to claim 1 , wherein the amino acids are selected from the group consisting of glycine, alanine, glutamic acid, L-arginine, lysine, L-cysteine, methionine and mixtures thereof.
3 . The composition according to claim 1 , wherein the pharmaceutically acceptable excipients selected from the group consisting of stabilizers, preservatives, sweetening agents, pH modifiers, pH adjusting agents, buffering agents, thickening agents, flavoring agents, and mixtures thereof.
4 . The composition according to claim 1 , wherein the solution is stable, such that the level of carbamoyloxyurea in the solution is less than 0.5% w/w as measured by HPLC, when the solution is stored at 2-8° C. for at least 12 months.
5 . The composition according to claim 1 , wherein the solution is free of sodium hydroxide, potassium hydroxide, sodium bicarbonate, or sodium carbonate as pH adjusters or pH modifiers.
6 . The composition according to claim 1 , wherein the solution resists pH change such that the pH remains within a range of 4.0 to 9.0.
7 . The composition according to claim 6 , wherein the pH remains within a range of 5.0 to 8.0.
8 . The composition according to claim 6 , wherein the pH remains within a range of 6.0 to 7.0.
9 . The composition according to claim 6 , wherein the pH remains within a range of 5.0 to 6.0.
10 . The composition according to claim 6 , wherein the pH remains within a range of 4.0 to 6.0.
11 . The composition according to claim 6 , wherein the pH remains within a range of 7.0 to 9.0.
12 . The composition according to claim 6 , wherein the pH remains within a range of 7.0 to 8.0.
13 . The composition according to claim 1 , wherein the pharmaceutically acceptable liquid vehicle is selected from group consisting of water, glycerin, alcohols, propylene glycol, polyethylene glycol, and mixtures thereof.
14 . The composition according to claim 1 , wherein the solution is free of preservatives.
15 . A pharmaceutical composition comprising:
(i) hydroxyurea at a concentration of about 10 mg/mL to about 100 mg/mL;
(ii) at least one pharmaceutically acceptable liquid vehicle;
(iii) one or more amino acids at a concentration of about 0.1 mg/mL to 10.0 mg/mL, and
(iv) 0.001% to 10% of one or more pharmaceutically acceptable excipients,
wherein the composition is in the form of a ready-to-use and safe-to-administer solution suitable for oral administration,
wherein the hydroxyurea is dissolved in the liquid vehicle and the solution is homogeneous, and
wherein the solution is stable, such that the level of carbamoyloxyurea in the solution is less than 0.5% w/w as measured by HPLC, when the solution is stored at 2-8° C. for at least 12 months.
16 . The pharmaceutical composition according to claim 1 , wherein the solution is free of sodium hydroxide, potassium hydroxide, sodium bicarbonate, or sodium carbonate as pH adjusters or pH modifiers.
17 . The pharmaceutical composition according to claim 15 , wherein the solution is free of sodium hydroxide, potassium hydroxide, sodium bicarbonate, or sodium carbonate as pH adjusters or pH modifiers.
18 . The pharmaceutical composition according to claim 1 , wherein the solution resists pH change such that the pH remains within a range of 4.0 to 6.0 or 7.0 to 9.0 when stored at 25° C./60% RH for at least 3 months.
19 . The pharmaceutical composition according to claim 15 , wherein the solution resists pH change such that the pH remains within a range of 4.0 to 6.0 or 7.0 to 9.0 when stored at 2-8° C. for at least 12 months.