Methods of treating autoimmune, respiratory and inflammatory disorders by inhalation of roflumilast n-oxide

Abstract

The present disclosure relates to pharmaceutical compositions useful for (and to a method of) treating autoimmune, respiratory and/or inflammatory diseases and conditions. The method involves administering to a subject in need thereof roflumilast N-oxide by inhalation. The present disclosure particularly relates to the treatment of asthma and chronic obstructive pulmonary disease (COPD) by administering roflumilast N-oxide by inhalation.

1 - 33 . (canceled) 
     
     
         34 . Roflumilast N-oxide having a d 90  of less than about 10 microns. 
     
     
         35 . The roflumilast N-oxide of  claim 34 , wherein the d 90  is less than about 6 microns. 
     
     
         36 . Roflumilast N-oxide having a d 90  equal to or less than 10 microns suitable for administration by inhalation. 
     
     
         37 . The roflumilast N-oxide of  claim 36 , having a d 90  of less than about 6 microns. 
     
     
         38 . The roflumilast N-oxide of  claim 34 , wherein the roflumilast N-oxide is in the form of a dry powder suitable for administration by inhalation. 
     
     
         39 . The roflumilast N-oxide of  claim 34 , wherein roflumilast N-oxide is in the form of a suspension. 
     
     
         40 . A pharmaceutical composition comprising micronized particles of roflumilast N-oxide or pharmaceutically acceptable salts thereof and, optionally, one or more pharmaceutically acceptable carriers and/or excipients, wherein the composition is suitable for administration by inhalation. 
     
     
         41 . The pharmaceutical composition of  claim 40 , wherein the pharmaceutical composition is in the form of an inhalable dry powder comprising micronized particles of roflumilast N-oxide or a pharmaceutically acceptable salt thereof as an active ingredient and particles of a physiologically acceptable pharmacologically inert solid carrier. 
     
     
         42 . The pharmaceutical composition of  claim 40 , wherein the pharmaceutical composition is in the form of an aerosol comprising micronized particles of roflumilast N-oxide or a pharmaceutically acceptable salt thereof as an active ingredient, a propellant and, optionally, one or more solvents, pharmaceutically acceptable carriers and/or excipients. 
     
     
         43 . The pharmaceutical composition of  claim 42 , wherein the roflumilast N-oxide is in the form of a suspension of particles of micronized roflumilast N-oxide in the propellant. 
     
     
         44 . The pharmaceutical composition of  claim 40 , wherein the d 50  or d 90  of the roflumilast N-oxide is less than about 10 microns. 
     
     
         45 . The pharmaceutical composition of  claim 40 , further comprising a long-acting β2 agonist, an M3 agonist, a corticosteroid, or any combination thereof. 
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein the long-acting β2 agonist is selected from carmoterol, GSK-642444, indacaterol, milveterol, arformoterol, formoterol, salbutamol, formoterol, levalbuterol, terbutaline, AZD-3199, BI-1744-CL, LAS-100977, bambuterol, isoproterenol, procaterol, clenbuterol, reproterol, fenoterol, ASF-1020, and any combination thereof. 
     
     
         47 . The pharmaceutical composition of  claim 45 , wherein the M3 antagonist is selected from aclidinium, tiotropium, ipratropium and oxitropium, and any combination thereof. 
     
     
         48 . The pharmaceutical composition of  claim 45 , wherein the corticosteroid is selected from the group consisting of dexamethasone, fluticasone, fluticasone furoate, prednisolone, betamethasone, budesonide, mometasone, mometasone furoate, triamcinolone acetonide, ciclesonide, TPI-1020, beclomethasone, beclomethasone dipropionate, prednisone, deflazacort, hydrocortisone, QAE-397, flunisolide, and any combination thereof. 
     
     
         49 . The pharmaceutical composition of  claim 40 , wherein the roflumilast N-oxide or pharmaceutically acceptable salt thereof is anhydrous, a solvate, or a hydrate. 
     
     
         50 . The pharmaceutical composition of  claim 40 , wherein the composition is contained within a metered dose inhaler (MDI) or a dry powder inhaler (DPI).