Stable ophthalmic formulations

Abstract

Disclosed herein are stable formulations suitable for the treatment of glaucoma and ocular hypertension.

1 . An ophthalmic composition for the treatment of glaucoma, ocular hypertension, or a combination thereof, the composition comprising a cyclodextrin and a therapeutically effective amount of a therapeutic component, wherein the composition has a pH between 5.8 and 6.5, and wherein the therapeutic component comprises dorzolamide or a pharmaceutically acceptable salt thereof and latanoprost. 
     
     
         2 . The composition according to  claim 1 , wherein the composition further comprises a mucoadhesive, a preservative, a pH-adjusting agent, a tonicity-adjusting agent, a buffering agent, an antioxidant, or a combination thereof. 
     
     
         3 . The composition according to  claim 1 , wherein the composition further comprises a therapeutically effective amount of an additional anti-glaucoma agent. 
     
     
         4 . The composition according to  claim 3 , wherein the additional anti-glaucoma agent is a beta blocker. 
     
     
         5 . The composition according to  claim 4 , wherein the beta blocker is timolol. 
     
     
         6 . The composition according to  claim 1 , wherein the pharmaceutically acceptable salt of dorzolamide is dorzolamide hydrochloride. 
     
     
         7 . The composition according to  claim 1 , wherein the cyclodextrin is hydroxypropyl-β-cyclodextrin. 
     
     
         8 . The composition according to  claim 2 , wherein the mucoadhesive is hyaluronic acid or a pharmaceutically acceptable salt thereof, polyvinyl alcohol, polyvinyl-pyrrolidone, hydroxypropyl-methylcellulose, carboxymethyl-cellulose, hydroxyethyl cellulose, a poloxamer, alginic acid, chitosan, xanthan gum, carrageenan, acrylic acid, acrylic acid derivatives, or a combination thereof. 
     
     
         9 . The composition according to  claim 2 , wherein the preservative is benzalkonium chloride, chlorobutanol, phenylmercuric acetate, phenylmercuric nitrate, polyhexinide, cetrimide, cetylpyridinium chloride, EDTA, or a combination thereof. 
     
     
         10 . The composition of  claim 2 , wherein the pH-adjusting agent is hydrochloric acid, boric acid, acetic acid, sodium hydroxide, potassium hydroxide, or a combination thereof. 
     
     
         11 . The composition of  claim 2 , wherein the tonicity-adjusting agent is sodium chloride, potassium chloride, mannitol, glycerol, sorbitol, xylitol, or a combination thereof. 
     
     
         12 . The composition of  claim 2 , wherein the buffering agent is an acetate buffer, a citrate buffer, a phosphate buffer, a borate buffer, or a combination thereof. 
     
     
         13 . The composition of  claim 2 , wherein the wherein the antioxidant is sodium metabisulfite, sodium thiosulfate, acetyl cysteine, BHA, BHT, vitamin E, ascorbic acid, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, or a combination thereof. 
     
     
         14 . The composition according to  claim 1 , wherein the composition comprises the following components in the following weight percentages: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   dorzolamide hydrochloride 
                   0.025-5% 
                 
                     
                   latanoprost 
                   0.001-5% 
                 
                     
                   HP-β-cyclodextrin 
                     0.01-50%. 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
               
            
           
         
       
     
     
         15 . The composition according to  claim 14 , wherein the composition comprises the following components in the following weight percentages: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   dorzolamide hydrochloride 
                   1-3% 
                 
                     
                   latanoprost 
                   0.003-0.01%  
                 
                     
                   HP-β-cyclodextrin 
                       2-10%. 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
               
            
           
         
       
     
     
         16 . An ophthalmic composition comprising a cyclodextrin and a therapeutically effective amount of a therapeutic component, wherein the composition has a pH in a range that maintains chemical, physical, and/or physiological stability of the therapeutic component and is well-tolerated by the eye, and wherein the therapeutic component comprises dorzolamide or a pharmaceutically acceptable salt thereof and latanoprost. 
     
     
         17 . The composition according to  claim 16 , wherein after 6 months of storage at 25° C., the composition comprises at least 97% of the initial amount of dorzolamide, and at least 98% of the initial amount of latanoprost. 
     
     
         18 . The composition according to  claim 16 , wherein after 6 months of storage at 40° C., the composition comprises at least 97% of the initial amount of dorzolamide, and at least 98% of the initial amount of latanoprost. 
     
     
         19 . A method of treating glaucoma comprising topically administering a composition according to  claim 1  to the eye of a patient in need thereof. 
     
     
         20 . A method of treating ocular hypertension comprising topically administering a composition according to  claim 1  to the eye of a patient in need thereof. 
     
     
         21 . A method of stabilizing an ophthalmic composition comprising dorzolamide or a pharmaceutically acceptable salt thereof and latanoprost, the method comprising incorporating a cyclodextrin into the formulation and adjusting the pH to a range that is well-tolerated by the eye and maintains stability of each of the active agents. 
     
     
         22 . The method according to  claim 21 , wherein after 6 months of storage at 25° C., the composition stabilized by the method comprises at least 97% of the initial amount of dorzolamide, and at least 98% of the initial amount of latanoprost. 
     
     
         23 . The composition according to  claim 22 , wherein after 6 months of storage at 40° C., the composition stabilized by the method comprises at least 97% of the initial amount of dorzolamide, and at least 98% of the initial amount of latanoprost. 
     
     
         24 . The composition according to  claim 21 , wherein the cyclodextrin is hydroxypropyl-β-cyclodextrin.