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.

What is claimed is:  
     
         1 . An aqueous cyclodextrin-free solution of meloxicam for administration by oral or parenteral route, 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 aqueous solution according to  claim 1 , wherein the meloxicam salt is the sodium or meglumine salt.  
     
     
         3 . The aqueous solution according to  claim 2 , wherein the solution contains meglumine and meloxicam in a molar ratio of between 9:8 and 12:8.  
     
     
         4 . The aqueous solution according to  claim 3 , wherein the solution contains meglumine and meloxicam in a molar ratio of 10:8.  
     
     
         5 . The aqueous solution according to one of  claims 1  to  4 , wherein the one or more suitable excipients is selected from the group consisting a buffer and a preservative.  
     
     
         6 . The aqueous solution according to  claim 5 , wherein the preservative is selected from the group consisting of ethanol; benzoic acid and the sodium and potassium salts thereof; sorbic acid and the sodium and potassium salts thereof, chlorobutanol; benzyl alcohol; phenylethanol; the methyl, ethyl, propyl, and butyl p-hydroxybenzoates; phenol; m-cresol; p-chloro-m-cresol; phenylmercury nitrate; and benzalkonium chloride.  
     
     
         7 . The aqueous solution according to  claim 5 , 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, and 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.  
     
     
         8 . The aqueous solution according to one of  claims 1  to  4 , wherein the one or more suitable excipients includes a solubilizer.  
     
     
         9 . The aqueous solution according to  claim 8 , wherein the solubilizer is selected from the group consisting of: polyethyleneglycols, polyoxyethylene-polyoxypropylene copolymers, glycofurol, arginine, lysine, castor oil, propyleneglycol, solketal, polysorbate, glycerol, sorbitol, mannitol, xylitol, polyvinylpyrrolidone, lecithin, cholesterol, 12-hydroxystearic acid-PEG660-ester, propyleneglycol monostearate, polyoxy-40-hydrogenated castor oil, polyoxyl-10-oleyl-ether, polyoxyl-20-cetostearylether, polyoxyl-40-stearate, and mixtures thereof.  
     
     
         10 . The aqueous solution according to one of  claims 1  to  4 , wherein the one or more suitable excipients is selected from the group consisting of: citric acid, lecithin, gluconic acid, tartaric acid, phosphoric acid, and EDTA and the alkali metal salts thereof.  
     
     
         11 . The aqueous solution according to one of  claims 1  to  4 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         12 . The aqueous solution according to  claim 5 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         13 . The aqueous solution according to  claim 6 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         14 . The aqueous solution according to  claim 7 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         15 . The aqueous solution according to  claim 8 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         16 . The aqueous solution according to  claim 9 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         17 . The aqueous solution according to  claim 10 , wherein the shelf-life of the solution after opening is 28 days or more at ambient temperature.  
     
     
         18 . The aqueous solution according to one of  claims 1  to  4 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         19 . The aqueous solution according to  claim 5 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         20 . The aqueous solution according to  claim 6 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         21 . The aqueous solution according to  claim 7 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         22 . The aqueous solution according to  claim 8 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         23 . The aqueous solution according to  claim 9 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         24 . The aqueous solution according to  claim 10 , wherein the solution has a long term shelf-life of 24 months or more at ambient temperature in its original packaging.  
     
     
         25 . The aqueous solution according to one of  claims 1  to  4 , wherein the solution has a pH of between 8.0 and 10.  
     
     
         26 . The aqueous solution according to  claim 1 , comprising meloxicam, meglumine, a polyethyleneglycol, a polyoxyethylene-polyoxypropylene copolymer, ethanol, glycine, disodium EDTA, and optionally sodium hydroxide or hydrochloric acid.  
     
     
         27 . The aqueous solution according to  claim 1 , consisting essentially of meloxicam, meglumine, a polyethyleneglycol, a polyoxyethylene-polyoxypropylene copolymer, ethanol, glycine, disodium EDTA, water suitable for injection, and optionally sodium hydroxide or hydrochloric acid.  
     
     
         28 . A method of treating pain, inflammation, fever, acute mastitis, diarrhea, lameness, problems with the locomotor apparatus, or respiratory complaints in a mammal, the method comprising administering to a mammal in need of such treatment the aqueous solution according to  claim 1 .  
     
     
         29 . The method according to  claim 28 , wherein the method is used in conjunction with antibiotic therapy.  
     
     
         30 . The method according to  claim 28 , wherein the solution according to  claim 1  is administered in dosage range of from 0.2 to 1.0 mg of active substance/kg of bodyweight of the mammal.  
     
     
         31 . The method according to claim  30 , wherein the solution according to  claim 1  is administered in dosage range of from 0.4 to 0.8 mg of active substance/kg of bodyweight of the mammal.  
     
     
         32 . The method according to claim  30 , wherein the solution according to  claim 1  is administered in dosage range of from 0.5 to 0.7 mg of active substance/kg of bodyweight of the mammal.