Administration of benzodiazepine compositions
View Patent ↗The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions.
1. A pharmaceutical solution for nasal administration consisting of:
(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) an alkyl glycoside.
2. The pharmaceutical solution of claim 1 , 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.
3. The pharmaceutical solution of claim 2 , wherein the benzodiazepine drug is diazepam, or a pharmaceutically-acceptable salt thereof.
4. The pharmaceutical solution of claim 1 , wherein said benzodiazepine is present in the pharmaceutical solution in a concentration from about 1 to about 20% (w/v).
5. The pharmaceutical solution of claim 4 , wherein said benzodiazepine is diazepam.
6. The pharmaceutical solution of claim 1 , wherein the one or more natural or synthetic tocopherols or tocotrienols are selected from the group consisting of: α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, tocophersolan, any isomers thereof, any esters thereof, any analogs or derivatives thereof, and any combinations thereof.
7. The pharmaceutical solution of claim 1 , 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).
8. The pharmaceutical solution of claim 1 , wherein the ethanol is present in the solution in a concentration of from 10 to 22.5% (w/v) and the benzyl alcohol is present in the solution in a concentration of from 7.5 to 12.5% (w/v).
9. The pharmaceutical solution of claim 8 , wherein the benzodiazepine is present in the pharmaceutical solution in a concentration from about 20 mg/mL to about 200 mg/mL.
10. The pharmaceutical solution of claim 1 , 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).
11. The pharmaceutical solution of claim 10 , 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).
12. The pharmaceutical solution of claim 1 , wherein the ethanol and benzyl alcohol are present in the pharmaceutical solution in a combined amount from about 15% to about 55% (w/w).
13. The pharmaceutical solution of claim 12 , wherein the ethanol and benzyl alcohol are present in the pharmaceutical solution in a combined amount from about 25% to about 40% (w/w).
14. The pharmaceutical solution of claim 1 , consisting of 5-15% (w/v) diazepam, 0.01-1% (w/v) alkyl glycoside, 45-65% (w/v) vitamin E, 10-25% (w/v) ethanol and 5-15% (w/v) benzyl alcohol.
15. The pharmaceutical solution of claim 1 , wherein the alkyl glycoside is present in pharmaceutical solution in a concentration of at least about 0.01% (w/w).
16. The pharmaceutical solution of claim 15 , wherein the alkyl glycoside is present in the pharmaceutical solution in an amount of 0.01% to 1% (w/w).
17. The solution of claim 1 , consisting of diazepam, vitamin E, ethanol, benzyl alcohol and dodecyl maltoside.
18. The solution of claim 17 , consisting of about 56.47% (w/v) vitamin E, about 10.5% (w/v) benzyl alcohol, about 10% (w/v) diazepam, about 0.25% (w/v) dodecyl maltoside, q.s. dehydrated ethanol.
19. The pharmaceutical solution of claim 14 , consisting of 5-15% (w/v) diazepam, 0.01-1% (w/v) dodecyl maltoside, 45-65% (w/v) vitamin E, 10-25% (w/v) ethanol and 5-15% (w/v) benzyl alcohol.
20. The pharmaceutical solution of claim 14 , consisting of 9-11% (w/v) diazepam, 0.1-0.5% (w/v) dodecyl maltoside, 50-60% (w/v) vitamin E, 15-22.5% (w/v) ethanol and 7.5-12.5 (w/v) benzyl alcohol.
21. The pharmaceutical solution of claim 14 , consisting of 10% (w/v) diazepam, 0.15-0.3% (w/v) dodecyl maltoside, 50-60 (w/v) vitamin E, 17-20% (w/v) ethanol and 10-12% (w/v) benzyl alcohol.
22. The solution of claim 16 , wherein the alkyl glycoside is dodecyl maltoside.