Sodium thiosulfate-containing pharmaceutical compositions
Provided herein are pharmaceutically acceptable sodium thiosulfate and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-purgeable organic carbon in a sodium thiosulfate-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium thiosulfate. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium thiosulfate.
1. A pharmaceutical composition comprising sodium thiosulfate pentahydrate and one or more pharmaceutically acceptable carriers or excipients, wherein the 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,
wherein the pharmaceutical composition is formulated for auricular administration.
2. The pharmaceutical composition of claim 1 , wherein the sodium thiosulfate pentahydrate has a positive identification test for sodium.
3. The pharmaceutical composition of claim 1 , wherein the sodium thiosulfate pentahydrate has a positive identification test for thiosulfate.
4. The pharmaceutical composition of claim 1 , wherein the composition is formulated as a single dosage form.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is water.
6. The pharmaceutical composition of claim 1 , further comprising one or more pH adjusting agents.
7. The pharmaceutical composition of claim 6 , further comprising one or more isotonic agents.
8. An oral dosage form comprising sodium thiosulfate pentahydrate and one or more pharmaceutically acceptable carriers or excipients, wherein the 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.
9. The oral dosage form of claim 8 , wherein the oral dosage form is a tablet, capsule, pill, troche, lozenge, pastille, cachet, pellet, medicated chewing gum, granule, bulk powder, effervescent or non-effervescent powder or granule, solution, emulsion, suspension, wafer, sprinkle, elixir, or syrup.
10. The oral dosage form of claim 8 , wherein the oral dosage form is a tablet.
11. The oral dosage form of claim 8 , wherein the oral dosage form is an enteric-coated tablet.
12. The oral dosage form of claim 8 , wherein the oral dosage form is a tablet coated with a fatty acid, fat, salicylate, wax, shellac, ammoniated shellac or cellulose acetate phthalate.
13. The oral dosage form of claim 8 , wherein the oral dosage form is a hard capsule.
14. The oral dosage form of claim 13 , wherein the hard capsule comprises gelatin, methylcellulose, starch or calcium alginate.
15. The oral dosage form of claim 8 , wherein the oral dosage form is a modified release dosage form comprising an erodible matrix device.
16. The oral dosage form of claim 15 , wherein the erodible matrix device comprises a water-swellable, erodible or soluble polymer.
17. The oral dosage form of claim 15 , wherein the erodible matrix device comprises hydroxypropyl methyl cellulose.