Pharmaceutical compositions comprising midazolam in a high concentration

Abstract

Compositions of midazolam, a benzodiazapine, in concentrations of 35-100 mg/ml are disclosed for the treatment of anxiety, epilepsy and epileptic seizures, invasive surgical procedures and diagnostic procedures and sedation. These compositions are particularly characterized by a solubilizer such an propylene glycol. Preferably, the compositions are aqueous solutions for intranasal administration.

1 - 37 . (canceled)  
     
     
         38 . A pharmaceutical composition for intranasal administration comprising midazalom or a pharmaceutically acceptable salt thereof, a solubilizer, and at least one of a sweetener, flavoring agent and masking agent.  
     
     
         39 . The pharmaceutical compositions of  claim 38  wherein the volume of the composition is 0.5 to 1.0 μl. (50-100 ml).  
     
     
         40 . The pharmaceutical composition of  claim 38  wherein the composition is preservative free.  
     
     
         41 . The pharmaceutical composition of  claim 38  comprising a buffer.  
     
     
         42 . The composition of  claim 38  wherein said at least one sweetener, flavoring agent and masking agent comprises saccharin, saccharin alkali salts, aspartame, acesulfame k, cyclamates, cyclidextrim and at least one of the flavorings of vanilla, mint, raspberry orange, caramel and cherry.  
     
     
         43 . The pharmaceutical compositions of  claim 38  wherein the pH is 2.5 to 7.  
     
     
         44 . A pharmaceutical composition for intranasal administration to a patient comprising an effective amount of midazalom or a pharmaceutically acceptable salt thereof, polyethylene glycol, saccharin and polypropylene glycol.  
     
     
         45 . The pharmaceutical composition of  claim 44  wherein the composition comprises a preservative.  
     
     
         46 . The pharmaceutical composition of  claim 44  wherein the composition is preservative free.  
     
     
         47 . The pharmaceutical composition of  claim 44  reaching a maximum plasma concentration in 3 to 15 minutes of nasal administration.  
     
     
         48 . The pharmaceutical composition of  claim 44  reaching a maximum plasma concentration of at least 40 ng.ml from a 0.06 mg/kg dose in each nostril.  
     
     
         49 . A method of treating a patient in need of sedation, anxiolysis or anesthesia comprising intranasally administering a composition comprising an effective amount of midazalom or a pharmaceutically acceptable salt thereof, and a solubilizer, wherein the induction of sedation, anxiolysis or anesthesia occurs within 3 to 15 minutes.  
     
     
         50 . A method of treating a patient in need of sedation, anxiolysis and anesthesia comprising intranasally administering to said patient an effective amount of a pharmaceutical composition comprising midazalom or a pharmaceutically acceptable salt thereof, a solubilizer, and at least one of a sweetener, flavoring agent or masking agent.  
     
     
         51 . The method of  claim 50  wherein at least one sweetener, flavoring agent or masking agent comprises saccharin, saccharin alkali salts, aspartame, acesulfame k, cyclamates, cyclidextrim and at least one of the flavorings of vanilla, mint, raspberry orange, caramel and cherry.  
     
     
         52 . The method of  claim 50  wherein the induction of sedation, anxiolysis and anesthesia occurs within 3 to 15 minutes after nasal administration of said composition.  
     
     
         53 . The method of  claim 50  wherein the induction of sedation, anxiolysis and anesthesia occurs at a maximum of plasma concentration reached within 3 to 15 minutes after nasal administration of said composition.