Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain

• US 8,865,743 B2
• Filed: 11/14/2007
• Issued: 10/21/2014
• Est. Priority Date: 01/06/2006
• Status: Active Grant

• Current Assignee: Vertical Pharmaceuticals LLC (Vertical/Trigen Holdings LLC)
• Original Assignee: AcelRx Pharmaceuticals Incorporated
• Inventors: Palmer, Pamela, Schreck, Thomas, Tzannis, Stelios, Hamel, Larry, Poutiatine, Andrew I., Rampersaud, Charles, Edwards, Bruce
• Primary Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US11/985,162
• Publication Number:
  US 20080268023A1
• Time in Patent Office: 2,533 Days
• Field of Search: 514/326
• US Class Current: 514/326
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

Compositions, systems and methods for administration of small volume sufentanil drug dosage forms to the sublingual mucosa of a subject for treatment of pain using a device are disclosed.

Claims

1. A method of treating pain by administering a tablet to the oral mucosa of a subject, said tablet comprising from about 5 to about 100 micrograms (mcg) of sufentanil expressed as the base and a bioadhesive material, wherein:

(i) said tablet adheres to the oral mucosa during the period of drug delivery;

(ii) said tablet has a volume of less than 30 microliters or a mass of less than 30 mg;

(iii) said tablet provides a dose-normalized mean Cmax of 1.59-2.75 pg/mL per mcg dosed; and

(iv) said tablet delivers a majority of the total amount of sufentanil in said tablet via the transmucosal route.

2. A method of treating pain by administering a tablet according to claim 1, wherein a single sublingual administration of said tablet to a subject results in a bioavailability of greater than 50%.

3. A method of treating pain by administering a tablet according to claim 1, wherein a single sublingual administration of said tablet to a subject results in a T_max with a coefficient of variation of less than 40%.

4. The method of treating pain according to claim 1, wherein a single sublingual administration of said tablet to a subject results in a mean T_max of from 0.68 to 0.89 hours.

5. A method of treating pain by administering a tablet according to claim 1, using a handheld dispensing device for placement of said tablet in the sublingual space.

6. The method of claim 5, wherein said tablet administration is patient controlled.

7. The method of claim 5, wherein said dispensing device comprises a housing having a dispensing end with a means to prevent or retard saliva ingress and a lock-out feature.

8. The method of claim 7, wherein said lock-out feature provides for repeated sublingual administration of sufentanil at a minimum interval of 20 minutes.

9. The method of claim 7, wherein said device further comprises a patient identification feature.

10. The method of claim 7, wherein said dispensing device further comprises a disposable cartridge which holds sufficient drug tablets to provide 48 to 72 hours of treatment.

11. The method of claim 10, wherein said cartridge includes a recognition system comprising a physical keyed feature on the cartridge, an optically detected feature or pattern, a bar code on the cartridge, a magnetic tag on the cartridge, an RFID tag on the cartridge, an electronic microchip on the cartridge, or a combination thereof which allows a dispensing device to recognize said cartridge.

12. The method of claim 1, wherein said tablet comprises a dose of sufentanil, expressed as the base, selected from the group consisting of 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and 100 mcg.

13. The method of claim 12, wherein said tablet comprises a 5 mcg dose of sufentanil expressed as the base.

14. The method of claim 12, wherein said tablet comprises a 10 mcg dose of sufentanil expressed as the base.

15. The method of claim 12, wherein said tablet comprises a 15 mcg dose of sufentanil expressed as the base.

16. The method of claim 12, wherein said tablet comprises a 20 mcg dose of sufentanil expressed as the base.

17. The method of claim 1, wherein erosion of said tablet is complete in from about 6 minutes to about 25 minutes following sublingual administration to said subject.

18. The method of claim 1, wherein said tablet delivers at least 55% of the total amount of sufentanil in said tablet via the transmucosal route.

19. The method of claim 16, wherein said tablet delivers at least 65% of the total amount of sufentanil in said tablet via the transmucosal route.

20. The method of claim 16, wherein said tablet delivers at least 75% of the total amount of sufentanil in said tablet via the transmucosal route.

21. The method of claim 1, wherein following administration of said tablet there is a linear relationship between C_max and the amount of sufentanil in said tablet.

22. The method of claim 13, wherein following administration of said dosage form there is a linear relationship between AUC_inf and the amount of sufentanil in said tablet.

23. The method of claim 1, wherein repeated sublingual administration of said tablet to a subject results in a T_max with a coefficient of variation of less than 40%.

24. A method of treating pain by administering a tablet to the oral mucosa of a subject, said tablet comprising from about 5 to about 100 micrograms (mcg) of sufentanil expressed as the base and a bioadhesive material, wherein:

(i) said tablet adheres to the oral mucosa during the period of drug delivery;

(ii) said tablet has a volume of less than 30 microliters or a mass of less than 30 mg; and

(iii) said tablet provides a mean Tmax of from 0.68 to 0.89 hours.

25. A method of treating pain by administering a tablet according to claim 24, wherein a single sublingual administration of said tablet to a subject results in a bioavailability of greater than 50%.

26. A method of treating pain by administering a tablet according to claim 24, wherein a single sublingual administration of said tablet to a subject results in a T_max with a coefficient of variation of less than 40%.

27. The method of treating pain according to claim 24, wherein a single sublingual administration of said tablet provides a dose-normalized mean C_max of 1.59-2.75 pg/mL per mcg dosed.

28. The method of treating pain according to claim 24, wherein said tablet delivers at least 55% of the total amount of sufentanil in said tablet via the transmucosal route.

29. The method of claim 24, wherein said tablet comprises a dose of sufentanil, expressed as the base, selected from the group consisting of 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and 100 mcg.

30. A method of treating pain by administering a tablet to the oral mucosa of a subject, said tablet comprising from about 5 to about 100 micrograms (mcg) of sufentanil expressed as the base and a bioadhesive material, wherein:

(i) said tablet adheres to the oral mucosa during the period of drug delivery;

(ii) said tablet has a volume of less than 30 microliters or a mass of less than 30 mg; and

(iii) said tablet delivers at least 55% of the total amount of sufentanil in said tablet via the transmucosal route.

31. The method of treating pain according to claim 30, wherein a single sublingual administration of said tablet provides a dose-normalized mean Cmax of 1.59-2.75 pg/mL per mcg dosed.

32. The method of treating pain according to claim 30, wherein a single sublingual administration of said tablet to a subject results in a mean Tmax of from 0.68 to 0.89 hours.

33. A method of treating pain by administering a tablet according to claim 30, wherein a single sublingual administration of said tablet to a subject results in a bioavailability of greater than 50%.

34. A method of treating pain by administering a tablet according to claim 30, wherein a single sublingual administration of said tablet to a subject results in a T_max with a coefficient of variation of less than 40%.

35. The method of claim 30, wherein said tablet comprises a dose of sufentanil, expressed as the base, selected from the group consisting of 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and 100 mcg.