Highly concentrated stable meloxicam solutions

Abstract

Aqueous cyclodextrin-free solution of meloxicam for administration by oral or parenteral route, containing a pharmacologically acceptable meloxicam salt of an organic or inorganic base and one or more suitable excipients, the content of dissolved meloxicam salt being more than 10 mg/mL. The formulation according to the invention has a shelf-life of up to 24 months or more.

We claim: 
     
         1 . A treatment method for treating a mammal suffering from one or more of pain, inflammation, fever, acute mastitis, diarrhea, lameness, locomotor deficiency, or respiratory illness, the method comprising administering to the mammal an aqueous, cyclodextrin-free solution comprising a pharmacologically acceptable meloxicam salt of an organic or inorganic base and one or more suitable excipients, wherein the concentration of dissolved meloxicam salt is more than 10 mg/mL. 
     
     
         2 . The method according to  claim 1 , wherein the method is used in conjunction with antibiotic therapy. 
     
     
         3 . The method according to  claim 1 , wherein the solution is administered in a dosage range of from 0.2 to 1.0 mg of active substance/kg of bodyweight of the mammal. 
     
     
         4 . The method according to  claim 1 , wherein the solution is administered in a dosage range of from 0.4 to 0.8 mg of active substance/kg of bodyweight of the mammal. 
     
     
         5 . The method according to  claim 1 , wherein the solution is administered in a dosage range of from 0.5 to 0.7 mg of active substance/kg of bodyweight of the mammal. 
     
     
         6 . A treatment method for treating an animal suffering from one or more of pain, inflammation, fever, acute mastitis, diarrhea, lameness, locomotor deficiency, or respiratory illness, the method comprising administering to the animal an aqueous, cyclodextrin-free solution comprising:
 a pharmacologically acceptable meloxicam salt; and   an excipient selected from the group consisting of citric acid, lecithin, gluconic acid, tartaric acid, phosphoric acid, and EDTA, and alkali metal salts thereof,   wherein the meloxicam salt is present in the aqueous solution in a concentration of more than 10 mg/mL.   
     
     
         7 . The treatment method according to  claim 6 , wherein the meloxicam salt is selected from the group consisting of meglumine salt, sodium salt, potassium salt, and ammonium salt. 
     
     
         8 . The treatment method according to  claim 7 , wherein the aqueous composition further comprises a solubilizer, a preservative, and a buffer 
     
     
         9 . The treatment method according to  claim 8 , wherein the solubilizer is selected from the group consisting of polyethyleneglycol, glycofurol, and polyoxyethylene-polyoxypropylene-copolymers. 
     
     
         10 . The treatment method according to  claim 8 , wherein the preservative is selected from the group consisting of ethanol, benzoic acid and the sodium or potassium salts thereof, and sorbic acid and the sodium or potassium salts thereof. 
     
     
         11 . The treatment method according to  claim 8 , wherein the buffer is effect to achieve a solution pH of between 8 and 10. 
     
     
         12 . The treatment method according to  claim 11 , wherein the buffer is selected from the group consisting of glycine, a mixture of glycine and HCl, a mixture of glycine and sodium hydroxide solution, the sodium and potassium salts thereof, a mixture of potassium hydrogen phthalate and hydrochloric acid, a mixture of potassium hydrogen phthalate and sodium hydroxide solution, and a mixture of glutamic acid and glutamate. 
     
     
         13 . The treatment method according to  claim 6 , wherein:
 the meloxicam salt is selected from the group consisting of meglumine or sodium salt of meloxicam;   the excipient is disodium EDTA; and   the aqueous further comprises:
 a solubilizer selected from the group consisting of polyethyleneglycols, glycofurol and polyoxyethylene-polyoxypropylene copolymers, 
 a preservative selected from the group consisting of ethanol, benzoic acid and the sodium or potassium salts thereof, and sorbic acid and the sodium or potassium salts thereof, and 
 a buffer selected from the group consisting of glycine, a mixture of glycine/HCl, and a mixture of glycine/sodium hydroxide solution, but preferably glycine. 
   
     
     
         14 . The treatment method according to  claim 13 , wherein:
 the meloxicam salt is present in a concentration of 11 mg/mL to 25 mg/mL;   the solubilizer is present in the range from 20 mg/mL to 200 mg/mL; and   the buffer is present in a concentration of from 4 mg/mL to 50 mg/mL.   
     
     
         15 . The treatment method according to  claim 6 , wherein:
 the meloxicam salt is meglumine; and   the aqueous further comprises:
 a solubilizer selected from the group consisting of polyethyleneglycols and polyoxyethylene-polyoxypropylene copolymers, 
 a preservative comprising ethanol, and 
 a buffer comprising glycine. 
   
     
     
         16 . The treatment method according to  claim 15 , wherein:
 the meglumine is present in a concentration of from 12.5 mg/mL to 16.5 mg/mL;   the ethanol is present in a concentration of from 100-200 mg/mL   
     
     
         18 . The treatment method according to  claim 6 , wherein:
 the meloxicam salt is present in a molar ratio of between 9:8 and 12:8; and   the excipient is present in a weight ratio of between 25:1 and 15:1.   
     
     
         19 . A kit comprising:
 packaging material; and   an aqueous, cyclodextrin-free solution comprising a pharmacologically acceptable meloxicam salt of an organic or inorganic base and one or more suitable excipients, wherein the concentration of dissolved meloxicam salt is more than 10 mg/mL,   wherein the solution is contained in the packaging material, and wherein shelf-life of the solution in the packaging material is from one month to 24 months.   
     
     
         20 . The kit according to  claim 19 , wherein the packaging material comprises a glass vial with a closure.