Administration of benzodiazepine compositions

Abstract

The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions.

1 - 65 . (canceled) 
     
     
         66 . A pharmaceutical solution for nasal administration comprising:
 a. a benzodiazepine drug;   b. one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, in an amount from about 30% to about 95% (w/w);   c. ethanol and benzyl alcohol in a combined amount from about 10% to about 70% (w/w); and   d. wherein the pharmaceutical solution is substantially free of water.   
     
     
         67 . The pharmaceutical solution of  claim 66 , wherein the benzodiazepine drug is selected from the group consisting of: alprazolam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepam, demoxazepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, any pharmaceutically-acceptable salts thereof, and any combinations thereof. 
     
     
         68 . The pharmaceutical solution of  claim 67 , wherein the benzodiazepine drug is diazepam, or a pharmaceutically-acceptable salt thereof. 
     
     
         69 . The pharmaceutical solution of  claim 66 , wherein the benzodiazepine drug is present in the pharmaceutical solution in a concentration from about 1 to about 20% (w/v). 
     
     
         70 . The pharmaceutical solution of  claim 69 , wherein the benzodiazepine drug is diazepam, or a pharmaceutically-acceptable salt thereof. 
     
     
         71 . The pharmaceutical solution of  claim 66 , wherein the one or more natural or synthetic tocopherols or tocotrienols are selected from the group consisting of: alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, delta-tocotrienol, tocophersolan, any isomers thereof, any esters thereof, any analogs or derivatives thereof, and any combinations thereof. 
     
     
         72 . The pharmaceutical solution of  claim 66 , wherein the ethanol is present in the pharmaceutical solution in a concentration of from 1 to 25% (w/v) and the benzyl alcohol is present in the pharmaceutical solution in a concentration from 1 to 25% (w/v). 
     
     
         73 . The pharmaceutical solution of  claim 66 , wherein the ethanol is present in the pharmaceutical solution in a concentration of from 10 to 22.5% (w/v) and the benzyl alcohol is present in the pharmaceutical solution in a concentration from 7.5 to 22.5% (w/v). 
     
     
         74 . The pharmaceutical solution of  claim 66 , wherein the benzodiazepine is present in the pharmaceutical solution in a concentration from about 20 mg/mL to about 200 mg/mL. 
     
     
         75 . The pharmaceutical solution of  claim 66 , wherein the one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, is in an amount from about 45% to about 85% (w/w). 
     
     
         76 . The pharmaceutical solution of  claim 75 , wherein the one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, is in an amount from about 50% to about 75% (w/w). 
     
     
         77 . The pharmaceutical solution of  claim 66 , wherein the ethanol and benzyl alcohol are present in the pharmaceutical solution in a combined amount from about 15% to about 55% (w/w). 
     
     
         78 . The pharmaceutical solution of  claim 77 , wherein the ethanol an benzyl alcohol are present in the pharmaceutical solution in a combined amount from about 25% to about 40% (w/w). 
     
     
         79 . The pharmaceutical solution of  claim 66 , comprising 5-15% (w/v) diazepam, 45-65% (w/v) vitamin E, 10-25% (w/v) ethanol, and 5-15% (w/v) benzyl alcohol. 
     
     
         80 . The pharmaceutical solution of  claim 66 , comprising diazepam, vitamin E, ethanol, and benzyl alcohol. 
     
     
         81 . The solution of  claim 80 , comprising about 56.47% (w/v) vitamin E, about 10.5% (w/v) benzyl alcohol, about 10% (w/v) diazepam, q.s. dehydrated ethanol. 
     
     
         82 . The pharmaceutical solution of  claim 66 , further comprising an alkyl glycoside. 
     
     
         83 . The pharmaceutical solution of  claim 82 , wherein the alkyl glycoside is present in the pharmaceutical solution in an amount of 0.01% to 1% (w/w). 
     
     
         84 . The pharmaceutical solution of  claim 82 , wherein the alkyl glycoside is dodecyl maltoside.