Ready-to-use ascorbic acid compound compositions
The invention described here provides ready-to-use (RTU) pharmaceutical compositions in single unit dose packaging, such compositions including ascorbic acid compound(s), such as sodium ascorbate, and one or more pharmaceutically acceptable excipients (e.g., a carrier and optionally other agents, such as a tonicity agent, a chelator, or both). The compositions provided by the invention are stable when stored at 20° C. to 25° C.±2° C. for at least about 3 months. Compositions provided by the invention comprise an osmolality of between about 270 mOsm/kg to about 340 mOsm/kg and do not require dilution or further manipulation prior to use. In certain aspects, the invention comprises methods of using such compositions in the treatment of diseases, conditions, or symptoms related to vitamin C deficiency, such as, in specific embodiments, scurvy.
1. An injectable, ready-to-use pharmaceutical composition comprising (a) a unit dose amount of an ascorbic acid compound component in a concentration of between about 20 mg/ml about 50 mg/ml, (b) one or more excipients, wherein the one or more excipients comprise (1) a chelation component consisting of an ethylenediaminetetraacetic acid (EDTA) compound or a suitable EDTA salt, (2) an antioxidant component consisting of a single antioxidant compound, and (3) a buffer in a concentration of between 1-1.5%; wherein there are no additional excipients present in the composition that exhibit antioxidant activity, wherein (c) the ready-to-use pharmaceutical composition has an osmolality of about 270 mOsm/kg to about 340 mOsm/kg, (d) the ready-to-use pharmaceutical composition does not require dilution prior to administration to a patient, (e) the ready-to-use pharmaceutical composition is stable according to United States Food and Drug Administration stability standards when stored at 20° C. to 25° C.±2° C. for at least 3 months prior to use, and (f) (I) the ready-to-use pharmaceutical composition has been demonstrated to be effective in treating scurvy in a statistically significant population of scurvy patients when administered in an effective daily dose for a sufficient period, (II) the ready-to-use pharmaceutical composition is bioequivalent to a second pharmaceutical composition, wherein the second pharmaceutical composition when administered to a population of scurvy patients results in a statistically significant number of the scurvy patients being effectively treated in one or more well controlled and adequate studies, or (III) both (I) and (II) are true.
2. The ready-to-use pharmaceutical composition of claim 1 , wherein the ascorbic acid compound component comprises sodium ascorbate.
3. The ready-to-use pharmaceutical composition of claim 1 , wherein the concentration of the ascorbic acid compound component in the composition is about 25 mg/mL.
4. The ready-to-use pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises an effective amount of a chelation component.
5. The ready-to-use pharmaceutical composition of claim 4 , wherein the ratio of the ascorbic acid compound component to the chelation component is less than or equal to about 1:0.00018 w/v.
6. The ready-to-use pharmaceutical composition of claim 4 , wherein the chelation component consists essentially of edetate disodium present in an amount of about 0.0005% w/v to about 0.15% w/v.
7. The ready-to-use pharmaceutical composition of claim 1 , wherein the one or more excipients comprises a tonicity component comprising one or more tonicity agent(s) selected from the group consisting of sodium chloride, dextrose, sucrose, xylitol, fructose, glycerol, sorbitol, mannitol, potassium chloride, mannose, calcium chloride, magnesium chloride, and suitable combinations of any two or more thereof.
8. The ready-to-use pharmaceutical composition of claim 7 , wherein the tonicity component comprises sodium chloride, dextrose, or sodium chloride and dextrose.
9. The ready-to-use pharmaceutical composition of claim 8 , wherein the composition comprises sodium chloride in an amount of about 0.1% w/v to about 0.9% w/v and dextrose in an amount of about 0.1% w/v to about 5% w/v.
10. The ready-to-use pharmaceutical composition of claim 1 , wherein the composition comprises a tonicity component, and wherein the ratio of the ascorbic acid compound component to the tonicity component in the composition is about 1:0.04-1:2 w/v.
11. The ready-to-use pharmaceutical composition of claim 1 , wherein the total amount of ascorbic acid compound component provided in the unit dose is between about 50 mg-about 390 mg.
12. The ready-to-use pharmaceutical composition of claim 1 , wherein the unit dose comprises between about 2 mL to about 10 mL of the composition.
13. The ready-to-use pharmaceutical composition of claim 1 , wherein the ready-to-use pharmaceutical composition is stable according to United States Food and Drug Administration stability standards when stored at 20° C. to 25° C.±2° C. for at least 12 months prior to use.
14. The ready-to-use pharmaceutical composition of claim 2 , wherein the ascorbic acid compound component consists essentially of sodium ascorbate.
15. The ready-to-use pharmaceutical composition of claim 9 , wherein the ratio of the ascorbic acid compound component to sodium chloride is less than about 1:0.5 w/v.
16. The ready-to-use pharmaceutical composition of claim 15 , wherein the ratio of the ascorbic acid compound component to sodium chloride is between about 1:0.04 and 1:0.36 w/v.