Sublingual buccal effervescent

• US 20020110578A1
• Filed: 02/20/2002
• Published: 08/15/2002
• Est. Priority Date: 03/27/1998
• Status: Active Grant

• Current Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cima Labs Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Robinson, Joseph R., Khankari, Rajendra K., Pather, Sathasivan Indiran, Eichman, Jonathan D., Hontz, John
• Granted Patent: US 6,974,590 B2
• Time in Patent Office: Days
• US Class Current: 424/434
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• 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 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

A pharmaceutical dosage form adapted to supply a medicament to the oral cavity for buccal, sublingual or gingival absorption of the medicament which contains an orally administerable medicament in combination with an effervescent for use in promoting absorption of the medicament in the oral cavity. The use of an additional pH adjusting substance in combination with the effervescent for promoting the absorption drugs is also disclosed.

Claims

1. A pharmaceutical dosage form for oral administration across an oral mucosa comprising:

a) a pharmaceutically effective amount of fentanyl or a pharmaceutically acceptable salt thereof; and

b) at least one saliva activated effervescent agent present in an amount sufficient to increase absorption of said pharmaceutically effective amount of fentanyl across the oral mucosa.

2. The dosage form of claim 1, further comprising at least one pH adjusting substance.

3. The dosage form of claim 2, wherein said pH adjusting substance is a base.

4. The dosage form of claim 3, wherein said base is selected from the group consisting of sodium carbonate, potassium carbonate, magnesium carbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium dihydrogen phosphate.

5. The dosage form of claim 1, further comprising a non-effervescent disintegration agent.

6. The dosage form of claim 5, wherein said non-effervescent disintegration agent is selected from the group consisting of microcrystalline cellulose, croscarmelose sodium, crospovidone, corn starch, potato starch, modified corn starch, modified potato starch, bentonite, alginates, agar, guar, locust bean, karaya, pecitin and tragacanth.

7. The dosage form of claim 1, further comprising a bioadhesive.

8. The dosage form of claim 1, further comprising glidants, lubricants, binders, sweeteners, flavoring and coloring components.

9. The dosage form of claim 1, wherein said pharmaceutically acceptable salt of fentanyl is fentanyl citrate.

10. A method of improving administration of fentanyl to a mammal, said method comprising administering said fentanyl or a pharmaceutically acceptable salt thereof to said mammal through an oral mucosa in a dosage form that also comprises at least one saliva activated effervescent agent in an amount sufficient to increase absorption of said fentanyl or pharmaceutically acceptable salt thereof across said oral mucosa.

11. The method of claim 10, wherein said fentanyl or pharmaceutically acceptable salt thereof is administered via a buccal route.

12. The method of claim 10, wherein said fentanyl or a pharmaceutically acceptable salt thereof is administered via a sublingual route.

13. The method of claim 10, wherein said fentanyl or a pharmaceutically acceptable salt thereof is administered via a gingival route.

14. The method of claim 10, wherein said mammal is a human.

15. The method of claim 10, wherein said dosage form is a tablet.

16. The method of claim 10, wherein said dosage form further includes a pH adjusting substance.

17. The method of claim 16, wherein said pH adjusting substance is a base.

18. The method of claim 16, wherein the amount of said pH adjusting substance is selected to provide a substantially neutral pH at a site of said absorption through said oral mucosa.

19. The method of claim 18, wherein said substantially neutral pH is higher than 7.