Novel compositions

• US 20060062812A1
• Filed: 09/12/2005
• Published: 03/23/2006
• Est. Priority Date: 03/11/2003
• Status: Abandoned Application

• Current Assignee: Sosei R&D Ltd.
• Original Assignee: Sosei R&D Ltd.
• Inventors: Booles, Clive, Ross, Calvin, Campbell, Alistair, Davis, Scott Andrew, Woodcock, Paul William
• Application Number:
  US11/224,383
• Publication Number:
  US 20060062812A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• 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 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Abstract

Compositions and method are provided, for the treatment of pain, e.g. acute breakthrough pain, by means of a systemic, non-invasive mode of administration. Specifically, the invention relates to a sublingual presentation of an opioid analgesic, such as fentanyl, or its salts, in amounts that are sufficient to treat the pain.

Claims

1. A pharmaceutical formulation having a pH of between about 7.4 and about 8.5, and comprising:

(a) fentanyl;

(b) water as carrier;

(c) a polar organic solvent in sufficient amount to enhance the solubility of the fentanyl in the water; and

(d) a buffer.

2. The formulation according to claim 1, wherein the fentanyl is present at a concentration of 0.1-10 mg/ml.

3. The formulation according to claim 1, wherein the polar organic solvent is selected from ethanol, propylene glycol, glycerol, polyethylene glycol and mixtures thereof.

4. The formulation according to claim 1, wherein the polar organic solvent is ethanol.

5. The formulation according to claim 1, wherein the polar organic solvent is present in an amount of 6-50% w/w.

6. The formulation according to claim 1, wherein the buffer is citrate buffer.

7. The formulation according to claim 1, which has pH around 8.2.

8. The formulation according to claim 1, which contains a sweetener.

9. The formulation according to claim 8, wherein the sweetener is saccharin.

10. The formulation according to claim 1, which contains menthol.

11. The formulation according to claim 1, wherein the fentanyl is introduced as the free base.

12. A metered dose dispensing system comprising a sealed container fitted with a metering pump, an actuator and a channelling device, wherein the container contains a pharmaceutical formulation having a pH of between about 7.4 and about 8.5, and comprising:

(a) fentanyl;

(b) water as carrier;

(c) a polar organic solvent in sufficient amount to enhance the solubility of the fentanyl in the water; and

(d) a buffer;

and wherein the system is adapted for sublingual administration of the formulation as a spray.

13. A pharmaceutical liquid composition comprising an opioid analgesic, the composition providing a plasma concentration of at least 250 pg/ml of opioid analgesic within a period of no more than 2 hours, following sublingual administration using a pump spray dispensing device.

14. The composition according to claim 13, wherein a plasma concentration of at least 250 pg/ml of opioid analgesic is achieved within a period of no more than 30 minutes.

15. The composition according to claim 13, wherein a plasma concentration of at least 250 pg/ml of opioid analgesic is achieved within a period of no more than 15 minutes.

16. The composition according to claim 13, wherein the opioid analgesic is fentanyl.

17. The composition according to claim 13, which is substantially free of any absorption enhancer.

18. The composition according to claim 13, which is substantially free of propellant.

19. The composition according to claim 16, wherein the fentanyl is present as the free base.

20. The composition according to claim 13, wherein the opioid analgesic is present at a concentration of 5 μ

g/ml to 50 mg/ml.

21. A method for providing analgesia or for the treatment of pain, which comprises administering sublingually, as a spray, a pharmaceutical liquid composition comprising an opioid analgesic, the composition providing a plasma concentration of at least 250 pg/ml of opioid analgesic within a period of no more than 2 hours, following sublingual administration using a pump spray dispensing device.

22. The method according to claim 21, wherein a volume of at least 60 μ

l and no more than 150 μ

l of the composition is administered to the sublingual area.

23. The method according to claim 21, wherein the composition has a bioavailability of more than 60% when delivered by a non-propellant pump spray device to the sublingual area.

24. The method according to claim 23, wherein the bioavailability is more than 70%.