COMPOSITIONS AND METHODS FOR TREATING MIDDLE-OF-THE-NIGHT INSOMNIA

• US 20100249177A1
• Filed: 06/08/2010
• Published: 09/30/2010
• Est. Priority Date: 05/25/2005
• Status: Active Grant

• Current Assignee: Paratek Pharmaceuticals Incorporated
• Original Assignee: Transcept Pharmaceuticals Incorporated
• Inventors: PATHER, SATHASIVAN I., SINGH, NIKHILESH N.
• Granted Patent: US 8,252,809 B2
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/0058 Chewing gums non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides compositions for treating middle-of-the-night insomnia without residual sedative effects upon awakening by administering low doses (about 5 mg or less) of zolpidem or a salt thereof.

Claims

1. A solid unit dosage composition for the treatment of MOTN insomnia, said composition comprising an effective amount of zolpidem or a salt thereof, formulated for delivery of zolpidem across a subject'"'"'s oral mucosa, wherein said effective amount is an amount of less than 1.30×

10−

5 moles of zolpidem, and is an amount sufficient to produce a plasma concentration between about 25 ng/ml and about 50 ng/ml within 20 minutes of administration, when evaluated in an appropriate patient population.

2. The solid unit dosage composition of claim 1, which further provides 50% of the maximum plasma concentration (Cmax) of zolpidem in 10 minutes or less.

3. The solid unit dosage composition of claim 2, which further provides blood levels of zolpidem that are less than 20 ng/ml at a time 4 hours after dosing.

4. The solid unit dosage composition of claim 1, further comprising at least one pH-adjusting agent selected from the group consisting of a carbonate salt and a bicarbonate salt.

5. The solid unit dosage composition of claim 1, further comprising a binary buffer system that raises the pH of said subject'"'"'s saliva to a pH greater than about 8.5, irrespective of the starting pH of saliva.

6. The solid unit dosage composition of claim 5, wherein the binary buffer system consists of sodium carbonate and sodium bicarbonate.

7. The solid unit dosage composition of claim 6, in the form of a quick-dissolving tablet or lozenge.

8. The solid unit dosage composition of claim 5, containing from 0.5 to 4.75 mg of zolpidem hemitartrate.

9. The solid unit dosage composition of claim 5, containing from 1.5 to 2.5 mg of zolpidem hemitartrate.

10. The solid unit dosage composition of claim 5, containing from 3.0 to 3.75 mg of zolpidem hemitartrate.

11. The solid unit dosage composition of claim 1, wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.

12. The solid unit dosage composition of claim 1, further comprising sodium stearyl fumarate.

13. A solid unit dosage composition for the treatment of MOTN insomnia, said composition comprising an amount of zolpidem or a salt thereof effective to produce sleep within 30 minutes of dosing a subject, but does not produce residual sedative effects when said subject is awakened at a time 4 hours after dosing, when the composition is evaluated in an appropriate patient population.

14. The solid unit dosage composition of claim 13, further comprising at least one pH-adjusting agent.

15. The solid unit dosage composition of claim 13, further comprising a binary buffer system.

16. The solid unit dosage composition of claim 15, wherein said binary buffer system consists of a carbonate salt and a bicarbonate salt.

17. The solid unit dosage composition of claim 15, in a dosage form for delivery of zolpidem across the subject'"'"'s oral mucosa, wherein said binary buffer system raises the pH of said subject'"'"'s saliva to a pH greater than about 8.5, irrespective of the starting pH of saliva.

18. The solid unit dosage composition of claim 17, containing less than 5 mg of zolpidem hemitartrate.

19. The solid unit dosage composition of claim 18, containing from 1.5 to 2.5 mg of zolpidem hemitartrate.

20. The solid unit dosage composition of claim 18, containing from 3.0 to 3.75 mg of zolpidem hemitartrate.

21. The solid unit dosage composition of claim 17, in the form of a quick-dissolving lozenge or tablet.

22. The solid unit dosage composition of claim 14, further comprising sodium stearyl fumarate.

23. A solid unit dosage composition for the treatment of MOTN insomnia, said composition comprising an effective amount of zolpidem or a salt thereof and at least one buffering agent, formulated for delivery of zolpidem across a subject'"'"'s oral mucosa, wherein said effective amount is 0.5 to 4.75 mg of zolpidem hemitartrate, and is an amount sufficient to produce a plasma concentration between about 25 ng/ml and about 50 ng/ml within 20 minutes of administration, when evaluated in an appropriate patient population.