Levothyroxine Formulations

Abstract

A levothyroxine composition includes levothyroxine sodium and mannitol. The composition is a lyophilized solid. The composition may include from 100 to 500 micrograms levothyroxine sodium and from 0.1 to 7 milligrams mannitol.

What is claimed is: 
     
         1 . A lyophilized solid composition, comprising:
 between 100 and 500 micrograms of a salt of levothyroxine;   a buffer; and   between 0.1 and 7 milligrams of mannitol.   
     
     
         2 . The lyophilized solid composition of  claim 1 , wherein, when the lyophilized solid composition is stored at 25° C. for a predetermined time period, less than 0.20% of the salt of levothyroxine is converted to liothyronine. 
     
     
         3 . The lyophilized solid composition of  claim 2 , wherein the predetermined time period is 12 months. 
     
     
         4 . The lyophilized solid composition of  claim 1 , wherein, when the lyophilized solid composition is stored at 40° C. for a predetermined time period, less than 0.20% of the salt of levothyroxine is converted to liothyronine. 
     
     
         5 . The lyophilized solid composition of  claim 4 , wherein the predetermined time period is 6 months. 
     
     
         6 . The lyophilized solid composition of  claim 1 , comprising between 1 and 5 milligrams of mannitol. 
     
     
         7 . The lyophilized solid composition of  claim 1 , wherein the buffer is a phosphate buffer. 
     
     
         8 . The lyophilized solid composition of  claim 7 , wherein the phosphate buffer is dibasic sodium phosphate in an amount between 400 and 600 micrograms. 
     
     
         9 . The lyophilized solid composition of  claim 1 , wherein the salt of levothyroxine is levothyroxine sodium. 
     
     
         10 . A pharmaceutical solution, comprising:
 the lyophilized solid composition of  claim 1 ; and   a pharmaceutically acceptable liquid carrier.   
     
     
         11 . The pharmaceutical solution of  claim 10 , wherein a concentration of the salt of levothyroxine in the pharmaceutical solution is between 5 and 500 μg/mL. 
     
     
         12 . The pharmaceutical solution of  claim 10 , wherein the pH of the pharmaceutical solution is between 9.5 and 11.5. 
     
     
         13 . A method of providing levothyroxine to a patient in need thereof, the method comprising:
 administering the pharmaceutical solution of  claim 10  to the patient in need thereof.   
     
     
         14 . The method of  claim 13 , wherein the pharmaceutical solution is administered to the patient in need thereof such that between about 50 to 500 micrograms of salt of levothyroxine is administered to the patient in need thereof. 
     
     
         15 . The method of  claim 14 , wherein the pharmaceutical solution is administered to the patient in need thereof such that between about 50 to 100 micrograms or about 300 to 500 micrograms of salt of levothyroxine is administered to the patient in need thereof. 
     
     
         16 . A method of preparing a lyophilized solid composition, the method comprising:
 (a) forming a liquid mixture comprising:
 a solvent, 
 a salt of levothyroxine, and 
 mannitol, 
   wherein the solvent comprises water and 1 to 20% by volume of an organic solvent; and   (b) freeze-drying the liquid mixture, thereby preparing the lyophilized solid composition.   
     
     
         17 . The method of  claim 16 , wherein the organic solvent is selected from the group consisting of ethanol, isopropanol, and t-butanol. 
     
     
         18 . The method of  claim 16 , wherein the mannitol comprises between 0.1 and 7 milligrams. 
     
     
         19 . The method of  claim 16 , wherein the salt of levothyroxine comprises between 100 and 500 micrograms. 
     
     
         20 . The method of  claim 16 , further comprises storing the lyophilized solid composition at 25° C. for a predetermined time period, wherein less than 0.20% of the salt of levothyroxine is converted to liothyronine following the predetermined time period.