System and method for intranasal administration of lorazepam

• US 6,610,271 B2
• Filed: 02/20/2001
• Issued: 08/26/2003
• Est. Priority Date: 05/10/2000
• Status: Expired due to Fees

• Current Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Original Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Inventors: Wermeling, Daniel P.
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Wells, Lauren Q.
• Application Number:
  US09/790,199
• Publication Number:
  US 20010055571A1
• Time in Patent Office: 917 Days
• Field of Search: 424/401, 424/44, 424/43, 514/219, 514/220
• US Class Current: 424/43
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics

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.

Claims

1. A pharmaceutical composition for intranasal administration to a mammal that produces a sedative-anxiolytic physiological response in the mammal, the composition consisting essentially of:

lorazepam;

polyethylene glycol and propylene glycol as a solvent-carrier for the lorazepam;

wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol constitutes from about 75% to about 85% by volume of the composition; and

a sweetener,

wherein the composition forms a spray when discharged from a manually actuated spray device.

2. The composition of claim 1, wherein the polyethylene glycol has an average molecular weight of about 400.

3. The composition of claim 1, wherein the polyethylene glycol constitutes about 20% by volume and the propylene glycol about 80% by volume of the composition.

4. The composition of claim 3, wherein the solvent-carrier is polyethylene glycol having an average molecular weight of about 400.

5. The composition of claim 3, wherein the lorazepam is present in the composition at a concentration of 1.0 mg/0.1 mL.

6. A sprayable liquid pharmaceutical composition for 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 consisting essentially of:

lorazepam;

polyethylene glycol and propylene glycol as a solvent for the lorazepam;

wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol constitutes from about 75% to about 85% by volume of the composition, a sweetener, and

a preservative,

wherein the lorazepam is present in the liquid composition at a concentration of about 1.0 mg/0.1 mL.

7. The composition of claim 6, wherein the polyethylene glycol has an average molecular weight of about 400.

8. The composition of claim 7, wherein the ratio of polyethylene glycol to propylene glycol is about four-to-one.

9. The composition of claim 7, wherein the solvent constitutes about 80% by volume and the propylene glycol about 18% by volume.

10. The composition of claim 6, wherein the sweetener is selected from the group consisting of saccharin and aspartame.

11. The composition of claim 10, wherein the sweetener is saccharin.

12. The composition of claim 6, wherein the preservative is butylated hydroxytoluene.

13. A method of treating a mammal exhibiting symptoms of anxiety-related disorders, said mammal requiring treatment, the method comprising the steps of:

a. providing an intranasal spray delivery device;

b. filling the delivery device with a sprayable liquid composition, the liquid composition consisting essentially of;

lorazepam, polyethylene glycol and propylene glycol as a solvent-carrier for the lorazepam;

wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol constitutes from about 75% to about 85% by volume of the composition, a sweetener, 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.

14. The method of claim 13, wherein the dose is administered by manually activating the delivery device.

15. The method of claim 13, wherein the predetermined dose is administered by spraying the lorazepam-containing composition first in one nostril and then in the other.

16. The method of claim 13, wherein the mammal is an adult human and the predetermined dose is two Mg of lorazepam.

17. The method of claim 13, wherein the sprayable liquid composition is prepared by dissolving lorazepam in the solvent carrier and adding the lorazepam in the solvent carrier to the delivery device under aseptic conditions.

18. The method of claim 13 which includes the further step of sterilizing the delivery device before addition of the liquid composition.

19. A pharmaceutical composition for intranasal administration consisting essentially of:

lorazepam;

polyethylene glycol and propylene glycol;

wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol constitutes from about 75% to about 85% by volume of the composition;

and a sweetener.

20. A composition according to claim 19, wherein the polyethylene glycol has an average molecular weight of about 400.

21. A composition according to claim 19, wherein the polyethylene glycol constitutes about 20% by volume and the propylene glycol about 80% by volume of the composition.

22. A composition according to claim 19, wherein the lorazepam is present in the composition at a concentration of 1.0 mg/0.1 ml.

23. The composition of claim 19, wherein the sweetener is saccharin, aspartame or combination thereof.

24. A pharmaceutical composition for intranasal administration consisting essentially of:

lorazepam;

polyethylene glycol and propylene glycol;

wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol constitutes from about 75% to about 85% by volume of the composition;

a sweetener, and a preservative.

25. A composition according to claim 24, wherein the sweetener is saccharin, aspartame or combination thereof.

26. A composition according to claim 24, wherein the preservative is butylated hydroxytoluene.

27. A pharmaceutical composition for intranasal administration consisting essentially of:

lorazepam 10.0 mg;

polyethylene glycol 400 0.18 mL;

propylene glycol 0.09 mL;

butylated hydroxytoluene 0.1 mg; and

saccharin 1.0 mg.

28. A method of treating a mammal suffering from anxiety comprising intranasally administering a pharmaceutical composition consisting essentially of:

lorazepam;

polyethylene glycol and propylene glycol;

wherein the polyethylene glycol constitutes from about 15% to about 25% by volume and the propylene glycol constitutes from about 75% to about 85% by volume of the composition;

a sweetener; and

a preservative, wherein the composition achieves a plasma lorazepam C_max of at least 21 ng/ml when administered intranasally.