Pharmaceutical composition comprising betahistine

Abstract

The present disclosure relates to a pharmaceutical composition comprising as active substance betahistine or a pharmaceutically acceptable salt thereof, for use in the treatment of otological or neurological disorders in a human subject by intranasal application.

1 - 59 . (canceled) 
     
     
         60 . A pharmaceutical composition for intranasal delivery to a human patient, comprising a solution or suspension of therapeutically effective amount of betahistine dihydrochloride and hydroxypropyl methylcellulose as a viscosity enhancing agent. 
     
     
         61 . The pharmaceutical composition of  claim 60 , wherein after a single intranasal administration to a human, the C max  of betahistine ranges from 80-125% of about 3000 pg/mL for a 5 mg betahistine dihydrochloride dose. 
     
     
         62 . The pharmaceutical composition of  claim 60 , wherein after a single intranasal administration to a human, the C max  of betahistine ranges from 80-125% of about 8000 pg/mL for a 10 mg betahistine dihydrochloride dose. 
     
     
         63 . The pharmaceutical composition of  claim 60 , wherein after a single intranasal administration to a human, the AUC 0-last  of betahistine ranges from about 80%-125% of about 1300 pg*hr/mL for a 5 mg betahistine dihydrochloride dose. 
     
     
         64 . The pharmaceutical composition of  claim 60 , wherein after a single intranasal administration to a human, the AUC 0-last  of betahistine ranges from about 80%-125% of about 3000 pg*hr/mL for a 20 mg betahistine dihydrochloride dose. 
     
     
         65 . The pharmaceutical composition of  claim 60 , wherein the t max  of betahistine in human plasma after single intranasal dose of the composition is about 0.08 h or greater. 
     
     
         66 . The pharmaceutical composition of  claim 60 , further comprising one or more moisturizing agent. 
     
     
         67 . The pharmaceutical composition of  claim 60 , wherein the one or more moisturizing agent is selected from the group consisting of glycerin, ethylene glycol, propylene glycol, propylene glycol 400, hexalene glycol, butylene glycol, dextrose, glyceryl triacetate, polydextrose, glycerol, glyceryl triacetate, sorbitol, mannitol, and combinations thereof. 
     
     
         68 . The pharmaceutical composition of  claim 67 , wherein the one or more moisturizing agent is selected from the group consisting of glycerin, polyethylene glycol 400 and propylene glycol. 
     
     
         69 . The pharmaceutical composition of  claim 60 , wherein the composition is in the form of a unit dose comprising the betahistine dihydrochloride in an amount of about 5 mg, about 10 mg, about 20 mg, about 40 mg, or about 80 mg. 
     
     
         70 . The pharmaceutical composition of  claim 60 , wherein the C max  of betahistine in human plasma after a single intranasal dose of the composition is at least about 3 ng/mL. 
     
     
         71 . The pharmaceutical composition of  claim 70 , wherein the single intranasal dose of the composition comprises about 5 mg, about 10 mg, about 20 mg, or about 40 mg of betahistine dihydrochloride. 
     
     
         72 . The pharmaceutical composition of  claim 60 , wherein the AUC 0-last  of betahistine in human plasma after a single intranasal dose of the composition is at least about 1200 hr*pg/mL. 
     
     
         73 . The pharmaceutical composition of  claim 72 , wherein the single intranasal dose of the composition comprises about 5 mg, about 10 mg, about 20 mg, or about 40 mg of betahistine dihydrochloride. 
     
     
         74 . The pharmaceutical composition of  claim 60 , further comprising at least one enzyme inhibitor or absorption promoter. 
     
     
         75 . The pharmaceutical composition of  claim 60 , wherein the pH of the composition is about 4.4 to about 6.4. 
     
     
         76 . The pharmaceutical composition of claim  1 , wherein the viscosity of the composition is about 1 cps to about 10 cps as measured by the USP <911> Viscosity method. 
     
     
         77 . A method of treating an inner ear disorder, vestibular disorder, neurotological disorder, otological disorder, neurological disorder, obesity, weight gain, or eating disorders in a subject in need thereof, comprising intranasally administering the pharmaceutical composition of  claim 60  to the subject. 
     
     
         78 . The method of  claim 77 , wherein the method is for treating a vestibular disorder. 
     
     
         79 . The method of  claim 78 , wherein the vestibular disorder is vestibular vertigo or Meniere's disease. 
     
     
         80 . The method of  claim 77 , wherein the method is for treating an inner ear disorder selected from tinnitus or hearing loss. 
     
     
         81 . The method of  claim 77 , wherein the method is for treating weight gain, wherein the weight gain is induced by administration of antipsychotic drugs acting on histamine receptors. 
     
     
         82 . The method of  claim 81 , wherein the antipsychotic drug is olanzapine.