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 . A ready-to-use pharmaceutical composition comprising:
(a) a unit dose amount of an ascorbic acid component comprising one or more ascorbic acid compounds, wherein the ascorbic acid component is present in the composition in a concentration of about 20 mg/mL-about 30 mg/mL; and
(b) an excipient component comprising:
(i) sodium bicarbonate in a concentration of about 10 mg/mL-about 15 mg/mL; and
ii) an ethylenediaminetetraacetic acid (EDTA) compound in a concentration that is effective to detectably enhance the stability of the composition, wherein the concentration of the EDTA compound in the composition is less than about 0.5 mg/mL, and
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 3 months prior to use; the composition does not contain sodium diethyldithiocarbamate, and wherein the composition is adapted for parenteral administration.
2 . The ready-to-use composition of claim 1 , wherein the EDTA compound is present in the composition in a concentration of about 0.01 mg/mL-about 0.5 mg/mL.
3 . The ready-to-use composition of claim 2 , wherein the EDTA compound is present in the composition in a concentration representing less than about 0.02 mg/mL.
4 . The ready-to-use pharmaceutical composition of claim 1 , wherein the excipient component of the composition does not comprise an excipient antioxidant component comprising a compound exhibiting an antioxidant effect.
5 . The ready-to-use composition of claim 4 , wherein the EDTA compound is present in the composition in a concentration of less than about 0.02 mg/mL.
6 . The ready-to-use composition of claim 1 , wherein the EDTA compound is present in the composition in a concentration equal to or greater than 0.06 mg/mL.
7 . The ready-to-use composition of claim 1 , wherein the one or more ascorbic acid compounds are present in the composition in a concentration of about 25 mg/mL.
8 . The ready-to-use composition of claim 2 , wherein the one or more ascorbic acid compounds are present in the composition in a concentration of about 25 mg/mL.
9 . The ready-to-use composition of claim 1 , wherein the excipient component of the composition further comprises an excipient antioxidant component, wherein the excipient antioxidant component consists of one antioxidant compound exhibiting an antioxidant effect.
10 . The ready-to-use composition of claim 8 , wherein the excipient component of the composition further comprises an excipient antioxidant component, wherein the excipient antioxidant component consists of one antioxidant compound exhibiting an antioxidant effect.
11 . The ready-to-use composition of claim 1 , wherein the excipient component of the composition further comprises an excipient antioxidant component, wherein the excipient antioxidant component consists of one antioxidant compound exhibiting an antioxidant effect, and wherein the antioxidant compound of the excipient antioxidant component exhibiting the antioxidant effect is present in an amount such that the weight ratio of the antioxidant compound exhibiting the antioxidant effect to any other compound present in the composition exhibiting an antioxidant effect is not 1:1.
12 . The ready-to-use composition of claim 8 , wherein the excipient component of the composition further comprises an excipient antioxidant component, wherein the excipient antioxidant component consists of one antioxidant compound exhibiting an antioxidant effect, and wherein the antioxidant compound of the excipient antioxidant component exhibiting the antioxidant effect is present in an amount such that the weight ratio of the antioxidant compound exhibiting the antioxidant effect to any other compound present in the composition exhibiting an antioxidant effect is not 1:1.
13 . The ready-to-use composition of claim 9 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is not sodium bisulfite, sodium formaldehyde sulfoxylate, or thiourea.
14 . The ready-to-use composition of claim 13 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is sodium metabisulfite.
15 . The ready-to-use composition of claim 14 , wherein the sodium metabisulfite is present in the composition in a concentration of about 0.5 mg/mL to about 2 mg/mL.
16 . The ready-to-use composition of claim 10 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is not sodium bisulfite, sodium formaldehyde sulfoxylate, or thiourea.
17 . The ready-to-use composition of claim 16 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is sodium metabisulfite.
18 . The ready-to-use composition of claim 17 , wherein the sodium metabisulfite is present in the composition in a concentration of about 0.5 mg/mL to about 2 mg/mL.
19 . The ready-to-use composition of claim 11 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is not sodium bisulfite, sodium formaldehyde sulfoxylate, or thiourea.
20 . The ready-to-use composition of claim 19 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is sodium metabisulfite.
21 . The ready-to-use composition of claim 20 , wherein the sodium metabisulfite is present in the composition in a concentration of about 0.5 mg/mL to about 2 mg/mL.
22 . The ready-to-use composition of claim 12 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is not sodium bisulfite, sodium formaldehyde sulfoxylate, or thiourea.
23 . The ready-to-use composition of claim 22 , wherein the antioxidant compound of the excipient antioxidant component demonstrating the antioxidant effect is sodium metabisulfite.
24 . The ready-to-use composition of claim 23 , wherein the sodium metabisulfite is present in the composition in a concentration of about 0.5 mg/mL to about 2 mg/mL.
25 . The ready-to-use composition of claim 1 , wherein the composition further comprises a pH adjustment component comprising sodium hydroxide.
26 . The ready-to-use composition of claim 25 , wherein the pH adjustment component further comprises hydrochloric acid.
27 . The ready-to-use composition of claim 1 , wherein (1) the 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 of time; (2) the 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 (3), the 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 of time and the 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.
28 . The ready-to-use composition of claim 3 , wherein (1) the 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 of time; (2) the 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 (3), the 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 of time and the 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.
29 . The ready-to-use composition of claim 4 , wherein (1) the 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 of time; (2) the 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 (3), the 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 of time and the 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.
30 . A method of treating scurvy comprising administering to a patient diagnosed with scurvy an effective amount of the composition of claim 1 .