System and method for intranasal administration of lorazepam

Abstract

A therapeutic composition of lorazepam and its pharmaceutically acceptable derivatives are provided for intranasal administration of at least one predetermined volumetric unit dose in the form of a spray by means that delivers one or more therapeutically prescribed unit doses that are highly accurate as to the volume discharged and which leave no significant quantity of the composition in the delivery means.

1 . A pharmaceutical composition for intranasal administration to a mammal in the form of a controlled unit-dose liquid spray to produce a pharmacologically induced sedative-anxiolytic physiological response in the mammal, the composition comprising: 
 lorazepam;    a physiologically acceptable non-aqueous, organic liquid solvent-carrier for the lorazepam; and    a preservative,    wherein the liquid composition forming a spray when discharged from a manually actuated spray device.    
     
     
         2 . The composition of  claim 1 , wherein the solvent-carrier is selected from the group consisting of polyethylene glycol, propylene glycol, and mixtures thereof.  
     
     
         3 . The sprayable composition of  claim 1 , wherein the solvent-carrier constitutes a minor proportion of the composition.  
     
     
         4 . The composition of  claim 2 , wherein the solvent carrier comprises polyethylene glycol having an average molecular weight of about 400.  
     
     
         5 . The composition of  claim 2 , wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol from about 75% to about 85% by volume of the liquid composition.  
     
     
         6 . The composition of  claim 5 , wherein the polyethylene glycol constitutes about 20% by volume and the polpylene glycol about 80% by volume of the liquid composition.  
     
     
         7 . The composition of  claim 6 , wherein the solvent-carrier is polyethylene glycol having an average molecular weight of about 400.  
     
     
         8 . The composition of  claim 6 , wherein the lorazepam is present at a concentration of 1.0 mg/0.1 mL of liquid.  
     
     
         9 . The composition of  claim 1  which further includes an additive selected from the group consisting of preservatives, artificial sweeteners, flavors, and combinations thereof.  
     
     
         10 . A sprayable liquid pharmaceutical composition for the controlled intranasal administration in the form of at least one unit-dose to a mammal for the purpose of producing a sedative-anxiolytic response in the mammal, the composition comprising: 
 lorazepam;    a physiologically acceptable non-aqueous solvent for the lorazepam; and    a preservative,    wherein the lorazepam is present in the liquid composition at a concentration of about 1.0 mg/0.1 mL.    
     
     
         11 . The composition of  claim 10  which further includes a physiologically acceptable liquid solute for the lorazepam solvent.  
     
     
         12 . The composition of  claim 11 , wherein the solute for the lorazepam solvent is propylene glycol water.  
     
     
         13 . The composition of  claim 12 , wherein the lorazepam solvent is polyethylene glycol having a number average molecular weight of about 400.  
     
     
         14 . The composition of  claim 13 , wherein the ratio of polyethylene glycol to propylene glycol is about four-to-one.  
     
     
         15 . The composition of  claim 13 , wherein the solvent constitutes about 80% by volume and the propylene glycol about 18% by volume.  
     
     
         16 . The composition of  claim 10  which further includes an artificial sweetener selected from the group consisting of saccharin and aspartame.  
     
     
         17 . The composition of  claim 16 , wherein the sweetener is saccharin.  
     
     
         18 . The composition of  claim 10  which further includes a preservative.  
     
     
         19 . The composition of  claim 18 , wherein the preservative is butglated hydroxytokrene.  
     
     
         20 . A method of treating a mammal exhibiting symptoms of anxiety-related disorders, said mammal requiring treatment, the method comprising the steps of: 
 a. providing a controlled dose intranasal spray delivery device;    b. filling the delivery device with a sprayable liquid composition, the liquid composition comprising: 
 lorazepam, a physiologically acceptable solvent-carrier for the lorazepam; and  
   c. administering a predetermined measured dose of the liquid lorazepam-containing composition intranasally to the mammal requiring treatment by spraying the liquid composition droplets from the delivery device into at least one of the mammal's nostrils.    
     
     
         21 . The method of  claim 20 , wherein the dose is administered by manually activating the delivery device.  
     
     
         22 . The method of  claim 20 , wherein the predetermined dose is administered by spraying the lorazepam-containing composition first in one nostril and then in the other.  
     
     
         23 . The method of  claim 20 , wherein the mammal is an adult human and the predetermined dose is two mg. of lorazepam.  
     
     
         24 . The method of  claim 20 , wherein the sprayable liquid composition is prepared by dissolving lorazepam in an organic solvent selected from the group consisting of polyethylene glycol 400, propylene glycol, and mixtures thereof, and adding the lorazepam solution to the delivery device under aseptic conditions.  
     
     
         25 . The method of  claim 20  which includes the further step of sterilizing the delivery device before addition of the liquid composition.