Controlled release corticosteroid compositions and methods for the treatment of otic disorders

Abstract

Disclosed herein are compositions and methods for the treatment of otic disorders with steroid, NSAID, and/or adenosine triphosphatase (“ATPase”) modulator agents. In these methods, the steroidal, NSAID, and/or ATPase compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of these compositions and formulations onto or via perfusion into the targeted auris structure(s).

1 .- 22 . (canceled) 
     
     
         23 . An intratympanic composition for use in the treatment of an otic disorder, the intratympanic composition comprising
 a multiparticulate anti-inflammatory corticosteroid; and   an auris acceptable carrier,   wherein sustained release of the anti-inflammatory corticosteroid into the cochlea occurs for a period of at least 5 days after a single administration.   
     
     
         24 . The intratympanic composition of  claim 23 , wherein the auris acceptable carrier comprises an auris acceptable surfactant. 
     
     
         25 . The intratympanic composition of  claim 24 , wherein the auris acceptable surfactant comprises a vegetable oil. 
     
     
         26 . The intratympanic composition of claim  21 , wherein the intratympanic composition is capable of being injected by a narrow gauge needle or cannula through the tympanic membrane to an area on or near the round window membrane. 
     
     
         27 . The intratympanic composition of claim  21 , wherein the intratympanic composition has an osmolarity of from about 100 mOsm/L to about 1000 mOsm/L. 
     
     
         28 . The intratympanic composition of claim  21 , wherein the multiparticulate anti-inflammatory corticosteroid is micronized anti-inflammatory corticosteroid. 
     
     
         29 . The intratympanic composition of claim  21 , wherein the intratympanic composition is not a hydrogel. 
     
     
         30 . The intratympanic composition of claim  21 , wherein the composition comprises between 1-70 mg/mL of the multiparticulate anti-inflammatory corticosteroid. 
     
     
         31 . The intratympanic composition of claim  21 , wherein the anti-inflammatory corticosteroid is dexamethasone, dexamethasone ester, or pharmaceutically acceptable salt thereof. 
     
     
         32 . The intratympanic composition of  claim 28 , wherein the anti-inflammatory corticosteroid is methylprednisolone, or pharmaceutically acceptable salt thereof. 
     
     
         33 . The intratympanic composition of  claim 28 , wherein the anti-inflammatory corticosteroid is prednisolone, or pharmaceutically acceptable salt thereof. 
     
     
         34 . The intratympanic composition of claim  21 , wherein the otic disorder is selected from Meniere's disease, Autoimmune ear disease (AIED), otitis media, acoustic trauma induced sensorineural hearing loss, drug induced sensorineural hearing loss, sensorineural hearing loss due to infection, idiopathic sensorineural hearing loss, vertigo, tinnitus, and combinations thereof. 
     
     
         35 . The intratympanic composition of  claim 34 , wherein the otic disorder is Meniere's disease. 
     
     
         36 . The intratympanic composition of  claim 34 , wherein the otic disorder is tinnitus. 
     
     
         37 . The intratympanic composition of claim  21 , wherein sustained release of the anti-inflammatory corticosteroid into the cochlea occurs for a period of at least 10 days after a single administration. 
     
     
         38 . The intratympanic composition of claim  21 , wherein sustained release of the anti-inflammatory corticosteroid into the cochlea occurs for a period of at least 14 days after a single administration. 
     
     
         39 . An intratympanic composition for use in the treatment of an otic disorder, the composition comprising:
 from 4.5 wt % to 6 wt % multiparticulate dexamethasone; and   an auris acceptable carrier;   wherein the composition has an osmolarity of 270-320 mOsm/L, and wherein sustained release of dexamethasone into the cochlea occurs for a period of at least 5 days after a single administration.   
     
     
         40 . The intratympanic composition of  claim 39 , wherein the multiparticulate dexamethsone is micronized dexamethasone. 
     
     
         41 . The intratympanic composition of  claim 39 , wherein the auris acceptable carrier comprises an auris acceptable surfactant, and wherein the auris acceptable surfactant comprises a vegetable oil. 
     
     
         42 . The intratympanic composition of  claim 39 , wherein the intratympanic composition is not a hydrogel.