Sublingual formulation of riluzole

Patent metadata

Field	Value
Publication number	US-11660267-B2
Application number	US-201515100160-A
Country	US
Kind code	B2
Filing date	Nov 17, 2015
Priority date	Nov 21, 2014
Publication date	May 30, 2023
Grant date	May 30, 2023

Abstract

Disclosed is sublingual administration of riluzole. In particular, a method for treating a neuropsychiatric disorder or symptom by administering a sublingual formulation of riluzole is provided. In addition, a method of relieving or reducing oral pain using the sublingual formulation of riluzole is disclosed.

First claim

We claim:

1. A sublingual formulation in the form of a lyophilized, tableted pharmaceutical composition that provides sublingual absorption of riluzole comprising a pharmaceutically effective amount of riluzole or a pharmaceutically acceptable salt thereof, said formulation further comprising gelatin as a tablet binder in an amount of 1-10% based on the total weight of the pharmaceutical composition, mannitol or sorbitol as a bulking agent in an amount of 2-4% based on the total weight of the pharmaceutical composition, and docusate sodium as a solubilizing agent in an amount of 0.01-0.5% based on the total weight of the pharmaceutical composition, wherein the sublingual formulation has a great C max an earlier or less T max , or a great AUC per milligram of the riluzole than the same dose of orally administered riluzole.

2. The sublingual formulation of claim 1 further comprising a flavoring agent.

3. The sublingual formulation of claim 1 further comprising a sweetener.

4. The sublingual formulation of claim 3 wherein said sweetener comprises sucralose.

5. A sublingual formulation in the form of a lyophilized, tableted pharmaceutical composition that provides sublingual absorption of riluzole comprising an effective amount of riluzole or a pharmaceutically acceptable salt, solvate, anomer, enantiomer, hydrate or prodrug thereof, said formulation further comprising gelatin as a tablet binder in an amount of 1-10% based on the total weight of the pharmaceutical composition, mannitol or sorbitol as a bulking agent in an amount of 2-4% based on the total weight of the pharmaceutical composition, and docusate sodium as a solubilizing agent in an amount of 0.01-0.5% based on the total weight of the pharmaceutical composition, said sublingual formulation in the form of a lyophilized, tableted pharmaceutical composition capable of providing an AUC at a dose of 35 mg 10 of from 110% to 180% of the AUC of an oral tablet formulation at a dose of 50 mg, said AUC being measured at 0.5 hours, 1 hour or 2 hours after administration as measured in accordance with Example 6.

6. The sublingual formulation of claim 5 which further comprises mint flavoring.

7. The sublingual formulation of claim 5 which further comprises sucralose.

8. A lyophilized, tableted pharmaceutical composition suitable for sublingual administration comprising riluzole in an amount of 5-25% based on the total weight of the pharmaceutical composition, gelatin as a tablet binder in an amount of 1-10% based on the total weight of the pharmaceutical composition, mannitol in an amount of 2-4% based on the total weight of the pharmaceutical composition, docusate sodium in an amount of 0.01-0.5% based on the total weight of the pharmaceutical composition, sucralose and mint flavoring; said composition capable of providing a higher AUC ratio than the predicted AUC ratio of an oral tablet formulation comprising 50 mg of riluzole, said AUC being measured at 0.5 hours, 1 hour or 2 hours as measured in accordance with Example 6.

9. The lyophilized, tableted pharmaceutical composition of claim 8 wherein the AUC 0-0.5 ratio for a lyophilized pharmaceutical composition comprising 35 mg of riluzole is about 180% of the predicted AUC 0-0.5 ratio of an oral tablet formulation comprising 50 mg of riluzole.

10. The lyophilized, tableted pharmaceutical composition of claim 8 wherein the AUC 0-1 ratio for a lyophilized pharmaceutical composition comprising 35 mg of riluzole is about 136% of the predicted AUC 0-1 ratio of an oral tablet formulation comprising 50 mg of riluzole.

11. The lyophilized, tableted pharmaceutical composition of claim 8 wherein the AUC 0-2 ratio for a lyophilized pharmaceutical composition comprising 35 mg of riluzole is about 110% of the predicted AUC 0-2 ratio of an oral tablet formulation comprising 50 mg of riluzole.

12. The lyophilized, tableted pharmaceutical composition of claim 8 comprising an effective amount of riluzole to provide a daily dose of 80 mg.

13. The lyophilized, tableted pharmaceutical composition of claim 12 comprising 40 mg of riluzole.

Assignees

• Biohaven Pharmaceutical Holding Company Ltd B
• Biohaven Therapeutics Ltd

Inventors

• Coric Vladimir
• Berman Robert
• Vladyka Ronald S
• Saleh Amgad
• Yu Danny

Classifications

• A61P25/22

  Anxiolytics · CPC title

• A61K31/428

  condensed with carbocyclic rings · CPC title

• A61K9/20

  Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} · CPC title

• A61K9/006 Primary

  Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays · CPC title

• A61P25/24

  Antidepressants · CPC title