Sodium nitrite-containing pharmaceutical compositions
Provided herein are pharmaceutically acceptable sodium nitrite and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-volatile organic carbon in a sodium nitrite-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium nitrite. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium nitrite.
1. A pharmaceutical composition comprising sodium nitrite and one or more pharmaceutically acceptable carriers or excipients, wherein the sodium nitrite contains no greater than 0.02% by weight of sodium carbonate, contains no greater than 10 ppm of an anti-caking agent, has a loss on drying of no greater than 0.25% by weight, wherein the water content is no greater than 0.5% by weight, wherein the heavy metal content is no greater than 10 ppm, contains no greater than 0.4% by weight of sodium nitrate, contains no greater than 0.005% by weight of insoluble matter, contains no greater than 0.005% by weight of chloride, contains no greater than 0.01% by weight of sulfate, contains no greater than 0.001% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 3 ppm of arsenic, contains no greater than 0.003% by weight of selenium, contains no greater than 5000 ppm of ethanol, contains no greater than 3000 ppm methanol, wherein the total non-volatile organic carbon content is no greater than 10 ppm, and contains no greater than 0.25 EU/mg of bacterial endotoxins,
wherein the pharmaceutical composition is formulated for intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular, intrasynovial, intravesical, or subcutaneous administration.
2. The pharmaceutical composition of claim 1 , wherein the sodium nitrite contains no less than about 98% by weight of sodium nitrite.
3. The pharmaceutical composition of claim 1 , wherein the sodium nitrite contains no less than about 99.8% by weight of sodium nitrite as measured by Ion Chromatography analysis.
4. The pharmaceutical composition of claim 3 , wherein the sodium nitrite is a white solid.
5. The pharmaceutical composition of claim 4 , wherein a 10% aqueous solution of the sodium nitrite at 25° C. has a pH value between 8 and 9.
6. The pharmaceutical composition of claim 5 , which has total aerobic count of microbial load of no greater than about 100 CFU/g and has total yeast and mold count of no greater than about 20 CFU/g.
7. The pharmaceutical composition of claim 1 , wherein the composition is formulated as a single dosage form.
8. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is water.
9. The pharmaceutical composition of claim 1 , further comprising one or more pH adjusting agents.
10. The pharmaceutical composition of claim 9 , further comprising one or more isotonic agents.
11. The pharmaceutical composition of claim 1 , formulated for intravenous administration.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intravenous injection, infusion, or implantation.
13. The pharmaceutical composition of claim 1 , formulated for intraarterial administration.
14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intraarterial injection, infusion, or implantation.
15. The pharmaceutical composition of claim 1 , formulated for intraperitoneal administration.
16. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intraperitoneal injection, infusion, or implantation.
17. The pharmaceutical composition of claim 1 , formulated for intrathecal administration.
18. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intrathecal injection, infusion, or implantation.
19. The pharmaceutical composition of claim 1 , formulated for intraventricular administration.
20. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intraventricular injection, infusion, or implantation.
21. The pharmaceutical composition of claim 1 , formulated for intraurethal administration.
22. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intraurethral injection, infusion, or implantation.
23. The pharmaceutical composition of claim 1 , formulated for intrasternal administration.
24. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intrasternal injection, infusion, or implantation.
25. The pharmaceutical composition of claim 1 , formulated for intracranial administration.
26. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intracranial injection, infusion, or implantation.
27. The pharmaceutical composition of claim 1 , formulated for intramuscular administration.
28. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intramuscular injection, infusion, or implantation.
29. The pharmaceutical composition of claim 1 , formulated for intrasynovial administration.
30. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intrasynovial injection, infusion, or implantation.
31. The pharmaceutical composition of claim 1 , formulated for intravesical administration.
32. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for intravesical injection, infusion, or implantation.
33. The pharmaceutical composition of claim 1 , formulated for administration by subcutaneous injection.
34. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a sterile aqueous solution intended for subcutaneous injection, infusion, or implantation.
35. A method for treating cyanide poisoning, comprising sequentially administering intramuscularly to a subject having cyanide poisoning: (1) a therapeutically effective amount of a sterile aqueous solution comprising the pharmaceutical composition of claim 1 ; and (2) a therapeutically effective amount of a sterile aqueous solution comprising pharmaceutical grade sodium thiosulfate pentahydrate.
36. A kit that includes: (1) a single unit dosage form comprising pharmaceutical grade sodium nitrite, wherein said pharmaceutical grade sodium nitrite contains no greater than 0.02% by weight of sodium carbonate, contains no greater than 10 ppm of an anti-caking agent, has a loss on drying of no greater than 0.25% by weight, wherein the water content is no greater than 0.5% by weight, wherein the heavy metal content is no greater than 10 ppm, contains no greater than 0.4% by weight of sodium nitrate, contains no greater than 0.005% by weight of insoluble matter, contains no greater than 0.005% by weight of chloride, contains no greater than 0.01% by weight of sulfate, contains no greater than 0.001% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 3 ppm of arsenic, contains no greater than 0.003% by weight of selenium, contains no greater than 5000 ppm of ethanol, contains no greater than 3000 ppm methanol, wherein the total non-volatile organic carbon content is no greater than 10 ppm, and contains no greater than 0.25 EU/mg of bacterial endotoxins;
and (2) a single unit dosage form comprising sodium thiosulfate pentahydrate, wherein said sodium thiosulfate pentahydrate contains no greater than 8 ppm of non-purgeable organic carbon, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 0.003% by weight of selenium, contains no less than 98% by weight of sodium thiosulfate on an anhydrous basis measured by ion chromatography, has a water content between 32% and 37% by weight, has a heavy metal content of no greater than 10 ppm, contains no greater than 200 ppm of chloride, contains no greater than 0.001% by weight of sulfide, contains no greater than 0.002% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.1% of sulfite, contains no greater than 0.5% of sulfate, contains no greater than 3 ppm of arsenic, contains no greater than 0.001% by weight of lead, has total aerobic count of microbial load of no greater than 100 CFU/g, has total yeast and mold count of no greater than 20 CFU/g, contains no greater than 0.02 EU/mg of bacterial endotoxins, contains no greater than 0.002% by weight of nitrogen compounds, contains no greater than 0.005% by weight of insoluble matter, contains no greater than 0.01% by weight of residual anti-caking agent, and contains no greater than ICH Q3C (R3) limits of organic volatile impurities, wherein a 10% aqueous solution of the solid sodium thiosulfate pentahydrate at 25° C. is colorless and has a pH between 6.0 and 8.0, and wherein the solid sodium thiosulfate pentahydrate is odorless crystals.