Sublingual formulation of riluzole
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.
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.