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

• US 8,535,714 B2
• Filed: 10/18/2011
• Issued: 09/17/2013
• 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, Hamel, Lawrence, Poutiatine, Andrew, Tzannis, Stelio
• Primary Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US13/276,165
• Publication Number:
  US 20120035216A1
• Time in Patent Office: 700 Days
• Field of Search: 424/464, 514/329
• US Class Current: 424/464
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Compositions, systems and methods for administration of small volume sufentanil drug dosage forms via the oral transmucosal route of a subject for treatment of pain.

Claims

1. A tablet comprising:

about 5 to about 200 μ

g sufentanil or pharmaceutically acceptable salts thereof (expressed as the free base of sufentanil),

60-95 wt % of one or more bulking agents,

1-5 wt % of one or more hydrogel forming excipients, and

1-10 wt % of one or more lubricants,

wherein;

said tablet has a volume less than about 30 μ

L, and when said tablet is adhered to the oral mucosa of a patient during the period of drug delivery;

a) at least 55% of the total amount of sufentanil in the tablet is delivered via the oral transmucosal route;

b) at least 90% of the total amount of sufentanil delivered to the patient, as measured by plasma concentration, is delivered via the oral transmucosal route;

c) said tablet provides a mean T_max of about 15 minutes to about 80 minutes;

d) said tablet provides a mean T_max with a coefficient of variation of less than 40%; and

e) said tablet provides a dose-normalized mean C_max of about 1.59-2.75 pg/mL per meg dosed.

2. The tablet of claim 1, wherein said tablet has a volume of less than about 10 μ

L.

3. The tablet of claim 1 wherein said one or more bulking agents are selected from the group consisting of mannitol, di-calcium phosphate, and combinations thereof.

4. The tablet of claim 1, wherein said one or more hydrogel forming excipients is hydroxypropylmethylcellulose.

5. The tablet of claim 1, wherein said lubricant is selected from the group consisting of stearic acid, magnesium stearate, and combinations thereof.

6. The tablet of claim 1, wherein:

wherein said one or more bulking agents are selected from the group consisting of mannitol, di-calcium phosphate, and combinations thereof,

said one or more hydrogel forming excipients is hydroxypropylmethylcellulose,

and said lubricant is selected from the group consisting of stearic acid, magnesium stearate, and combinations thereof.

7. The tablet of claim 1, wherein the amount of sufentanil or pharmaceutically acceptable salts thereof is about 5 μ

g, 10 μ

g, 15 μ

g, 20 μ

g, 30 μ

g, 40 μ

g, 50 μ

g, 60 μ

g, 70 μ

g, 80 μ

g, 100 μ

g or 120 μ

g (expressed as the free base of sufentanil).

8. The tablet of claim 7, wherein the amount of sufentanil or pharmaceutically acceptable salts thereof is about 15 μ

g (expressed as the free base of sufentanil).

9. The tablet of claim 7, wherein the amount of sufentanil or pharmaceutically acceptable salts thereof is about 20 μ

g (expressed as the free base of sufentanil).

10. The tablet of claim 7, wherein the amount of sufentanil or pharmaceutically acceptable salts thereof is about 30 μ

g (expressed as the free base of sufentanil).

11. The tablet of claim 1, wherein after administration of said tablet to said subject, said tablet provides a mean T_max range of from about 30 minutes to about 70 minutes.

12. The tablet of claim 1, wherein after administration of said tablet to said subject, said tablet provides a mean T_max range of from about 40 minutes to about 55 minutes.

13. The tablet of claim 1, wherein after administration of said tablet to said subject, said tablet provides a mean T_max range of from about 35 minutes to about 60 minutes.

14. The tablet of claim 1, wherein after administration of said tablet to said subject, said tablet provides a mean T_max with a coefficient of variation of less than 30%.

15. The tablet of claim 1, wherein after administration of said tablet to said subject, at least 60% of the total amount of drug in said tablet is absorbed via the oral transmucosal route.

16. The tablet of claim 1, wherein after administration of said tablet to said subject, at least 70% of the total amount of drug in said tablet is absorbed via the oral transmucosal route.

17. The tablet of claim 1, wherein after administration of said tablet to said subject, at least 95% of the sufentanil delivered to the patient, as measured by plasma concentration, is delivered via the oral transmucosal route.

18. A method of treating pain, comprising administering the tablet of claim 1 to a patient in need thereof.

19. The method of claim 18, wherein said administering is by adhering said tablet to the sublingual membrane of said patient.

20. The method of claim 18, wherein said tablet has a volume of less than about 10 μ

L.

21. The method of claim 18, wherein said tablet is administered using a device.

22. A method of treating pain, comprising administering the tablet of claim 6 to a patient in need thereof.

23. A method of treating pain, comprising administering the tablet of claim 8 to a patient in need thereof.

24. The method of claim 23, wherein said tablet has a volume of less than about 10 μ

L.

25. The method of claim 23, wherein said tablet is administered using a device.