Nasal and Ophthalmic Delivery of Aqueous Corticosteroid Solutions

Abstract

The present invention is directed to methods of treating nasal and/or ophthalmic diseases, symptoms, or disorders that are therapeutically responsive to corticosteroid therapy by delivering aqueous solution formulations comprising a corticosteroid to nasal and ophthalmic tissues. The invention is also directed to methods, systems, devices, and compositions for delivering aqueous solution formulations comprising a corticosteroid and an antihistamine to nasal and ophthalmic tissues.

1 . A method for treating an allergic symptom or disorder in a subject in need thereof, comprising: nasally administering to the subject a corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier,
 wherein the allergic symptom or disorder includes a non-nasal symptom selected from the group consisting of itchy/gritty eyes, tearing/watery eyes, red/burning eyes, itchy ears/palate and combinations thereof.   
     
     
         2 . The method of  claim 1 , wherein the allergic symptom or disorder further comprises symptoms selected from the group consisting of runny nose, itchy nose, nasal congestion, sneezing and combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein said corticosteroid solution further comprises a therapeutically effective amount of an antihistamine. 
     
     
         4 . The method of  claim 3 , wherein the antihistamine is azelastine, olopatadine pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof; the corticosteroid is budesonide; and the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β-cyclodextrin). 
     
     
         5 . The method of  claim 4 , wherein the azelastine is present in an amount of about 30 μg to about 275 μg per unit dose, or the olopatadine is present in an amount of about 150 μg to about 1400 μg per unit dose, the budesonide is present in an amount of about 5 μg to about 500 μg per unit dose, and the CAPTISOL is present in an amount of 100 μg to 100 mg per unit dose. 
     
     
         6 . The method of  claim 1 , wherein the corticosteroid solution is administered 1-2 times per day. 
     
     
         7 . A method for treating an ocular symptom or disorder in a subject in need thereof, comprising: nasally administering to the subject a corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier,
 wherein the allergic symptom or disorder includes a non-nasal symptom selected from the group consisting of itchy/gritty eyes, tearing/watery eyes, red/burning eyes, itchy ears/palate and combinations thereof.   
     
     
         8 . The method of  claim 7 , wherein said corticosteroid solution further comprises a therapeutically effective amount of an antihistamine. 
     
     
         9 . The method of  claim 8 , wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof; the corticosteroid is budesonide; and the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β-cyclodextrin). 
     
     
         10 . The method of  claim 9 , wherein the azelastine is present in an amount of about 30 μg to about 275 μg per unit dose or the olopatadine is present in an amount of about 150 μg to about 1400 μg per unit dose, the budesonide is present in an amount of about 5 μg to about 500 μg per unit dose, and the CAPTISOL is present in an amount of 100 μg to 100 mg per unit dose. 
     
     
         11 . The method of  claim 7 , wherein the corticosteroid solution is administered 1-2 times per day. 
     
     
         12 . A method for treating ocular inflammation in a subject in need thereof, comprising: ophthalmically administering to the subject a corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier,
 wherein the corticosteroid solution provides more rapid reduction in ocular inflammation compared with a corticosteroid suspension at the same unit dose.   
     
     
         13 . The method of  claim 12 , wherein said corticosteroid solution further comprises a therapeutically effective amount of an antihistamine. 
     
     
         14 . The method of  claim 13 , wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof; the corticosteroid is budesonide; and the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β-cyclodextrin). 
     
     
         15 . The method of  claim 14 , wherein the azelastine is present in an amount of about 30 μg to about 275 μg per unit dose or the olopatadine is present in an amount of about 150 μg to about 1400 μg per unit dose, the budesonide is present in an amount of about 5 μg to about 500 μg per unit dose, and the CAPTISOL is present in an amount of 100 μg to 100 mg per unit dose. 
     
     
         16 . The method of  claim 12 , wherein the corticosteroid solution is administered 1-2 times per day. 
     
     
         17 . A metered dose device for nasal or ophthalmic administration comprising: corticosteroid solution comprising a therapeutically effective amount of corticosteroid, a therapeutically effective amount of an antihistamine, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier. 
     
     
         18 . The device of  claim 17 , wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof; the corticosteroid is budesonide; and the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β-cyclodextrin). 
     
     
         19 . The device of  claim 18 , wherein the azelastine is present in an amount of about 30 μg to about 275 μg per unit dose or the olopatadine is present in an amount of about 150 μg to about 1400 μg per unit dose, the budesonide is present in an amount of about 5 μg to about 500 μg per unit dose, and the CAPTISOL is present in an amount of 100 μg to 100 mg per unit dose. 
     
     
         20 . A system for treating an allergic symptom comprising: corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, a therapeutically effective amount of an antihistamine, SAE-CD and a pharmaceutically acceptable aqueous liquid carrier, and a metered dose device for nasal or ophthalmic administration of the corticosteroid solution to the subject. 
     
     
         21 . The system of  claim 20 , wherein the allergic symptom is selected from the group consisting of runny nose, itchy nose, nasal congestion, sneezing, itchy/gritty eyes, red/burning eyes, tearing/watery eyes and itchy ears/palate and combinations thereof. 
     
     
         22 . The system of  claim 21 , wherein the allergic symptom is selected from the group consisting of itchy/gritty eyes, tearing/watery eyes, red/burning eyes, itchy ears and palate and combinations thereof. 
     
     
         23 . The system of  claim 20 , wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof; the corticosteroid is budesonide; and the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β-cyclodextrin). 
     
     
         24 . The system of  claim 23  wherein the azelastine is present in an amount of about 30 μg to about 275 μg per unit dose or the olopatadine is present in an amount of about 150 μg to about 1400 μg per unit dose, the budesonide is present in an amount of about 5 μg to about 500 μg per unit dose, and the CAPTISOL is present in an amount of 100 μg to 100 mg per unit dose.