ANHYDROUS SODIUM THIOSULFATE AND FORMULATIONS THEREOF
Described herein is anhydrous sodium thiosulfate, methods for synthesizing anhydrous sodium thiosulfate, pharmaceutical compositions thereof, and methods of treating ototoxicity. Anhydrous sodium thiosulfate is synthesized from sodium sulfite, sulfur, and cetylpyridinium chloride. The anhydrous sodium thiosulfate is formulated into a pharmaceutical composition comprising a buffer and solvent. These compositions are useful for eliminating or reducing ototoxicity in pediatric patients receiving platinum-based chemotherapeutics.
1 . An aqueous anhydrous sodium thiosulfate solution wherein the sodium thiosulfate consists essentially of anhydrous sodium thiosulfate that is characterized by at least the following X-ray powder diffraction (XRPD) peaks before being solubilized in an aqueous solvent:
10.52, 15.13, 17.71, 19.70, 21.09, 21.49, 21.84, 27.40, 28.96, 30.46, 31.81, 32.52, 33.15, 37.40, and 38.16 degrees 2θ±0.2 degrees 2θ;
when the XRPD is collected from about 2 to about 40 degrees 2θ using copper Kα radiation.
2 . A pharmaceutical composition comprising an aqueous anhydrous sodium thiosulfate solution wherein the sodium thiosulfate consists essentially of anhydrous sodium thiosulfate that is characterized by at least the following X-ray powder diffraction (XRPD) peaks before being solubilized in an aqueous solvent:
10.52, 15.13, 17.71, 19.70, 21.09, 21.49, 21.84, 27.40, 28.96, 30.46, 31.81, 32.52, 33.15, 37.40, and 38.16 degrees 2θ±0.2 degrees 2θ;
when the XRPD is collected from about 2 to about 40 degrees 2θ using copper Kα radiation;
and wherein the pharmaceutical composition also comprises one or more pharmaceutically acceptable excipients.
3 . The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient selected from boric acid or a salt thereof, glycine or a salt thereof, tris(hydroxymethyl)aminomethane (tromethamine) or a salt thereof, or phosphate or a salt thereof.
4 . The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition comprises boric acid or a salt thereof.
5 . The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition comprises aqueous anhydrous sodium thiosulfate at a concentration between about 0.1 M and about 2 M.
6 . The pharmaceutical composition of claim 2 , comprising aqueous anhydrous sodium thiosulfate at a concentration between about 0.1 M to about 2 M and sodium phosphate, boric acid, glycine, or tris(hydroxymethyl)aminomethane (tromethamine) at a concentration between about 0.001 M to about 0.5 M.
7 . The pharmaceutical composition of claim 2 , wherein the aqueous anhydrous sodium thiosulfate is at a concentration of about 0.5 M.
8 . The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition comprises boric acid at a concentration of about 0.004 M.
9 . The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises boric acid at a concentration of about 0.004 M.
10 . The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition has a total volume of about 100 mL and is a clear, colorless, and sterile aqueous solution.