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

• US 20080268023A1
• Filed: 11/14/2007
• Published: 10/30/2008
• Est. Priority Date: 01/06/2006
• Status: Active Grant

• Current Assignee: Vertical Pharmaceuticals LLC (Vertical/Trigen Holdings LLC)
• Original Assignee: AcelRx Pharmaceuticals Incorporated
• Inventors: Edwards, Bruce, Tzannis, Stelios, Schreck, Thomas, Hamel, Larry, Palmer, Pamela, Rampersaud, Charles, Poutiatine, Andrew I.
• Granted Patent: US 8,865,743 B2
• Time in Patent Office: Days
• US Class Current: 424/435
• 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 dosage form for sublingual administration to a subject, comprising:

about 5 to about 100 micrograms (mcg) of sufentanil and a bioadhesive material, wherein said bioadhesive material provides for adherence to the sublingual mucosa of said subject and said dosage form has a volume of less than 30 microliters or a mass of less than 30 mg.

2. The drug dosage form according to claim 1, wherein said dosage form comprises a dose of sufentanil 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.

3. The drug dosage form according to claim 1, wherein erosion of said dosage form is complete in from about 6 minutes to about 25 minutes following sublingual administration to said subject.

4. The drug dosage form according to claim 1, wherein said dosage form is effective to deliver at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or at least 99% of the total amount of sufentanil in said dosage form via the sublingual route.

5. The drug dosage form according to claim 1, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 50%.

6. The drug dosage form according to claim 1, wherein a single sublingual administration of said dosage form to a subject results in an AUC_inf with a coefficient of variation of less than 40%.

7. The drug dosage form according to claim 1, wherein a single sublingual administration of said dosage form to a subject results in a T_max with a coefficient of variation of less than 40%.

8. The drug dosage form according to claim 1, wherein following administration of said dosage form there is a linear relationship between C_max and the amount of sufentanil in said dosage form.

9. The drug dosage form according to claim 1, wherein following administration of said dosage form there is a linear relationship between AUC_inf and the amount of sufentanil in said dosage form.

10. The drug dosage form according to claim 1, wherein following repeated sublingual administration of said dosage form to a subject, the bioavailability is greater than the bioavailability following a single sublingual administration to said subject.

11. The drug dosage form according to claim 1, wherein the difference between the T_max following repeated sublingual administration and the time of the previous sublingual administration is shorter than the T_max following a single sublingual administration to said subject.

12. The drug dosage form according to claim 1, wherein repeated sublingual administration of said dosage form to a subject results in a T_max with a coefficient of variation of less than 40%.

13. A method of treating pain by administering a dosage form according to claim 1 to a subject, wherein following administration of said dosage form there is a linear relationship between C_max and the amount of sufentanil in said dosage form.

14. A method of treating pain by administering a dosage form according to claim 1, wherein a single sublingual administration of sufentanil to a subject results in a bioavailability of greater than 50%.

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

16. A method of treating pain by administering a dosage form according to claim 1, wherein following repeated sublingual administration of said dosage form to a subject, the bioavailability is greater than the bioavailability following a single sublingual administration of said dosage form.

17. A method of treating pain by administering a dosage form according to claim 1, wherein the difference between the T_max following repeated sublingual administration and the time of the previous sublingual administration is shorter than the T_max following a single sublingual administration to said subject.

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

20. The method of claim 19, wherein said dosage form administration is patient controlled.

21. The method of claim 19, 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.

22. The method of claim 21, wherein said lock-out feature provides for repeated sublingual administration of sufentanil at a minimum interval of 20 minutes.

23. The method of claim 21, wherein said device further comprises a patient identification feature.

24. The method of claim 21, wherein said dispensing device further comprises a disposable cartridge configured to hold one or more drug dosage forms.

25. The method of claim 24, wherein said cartridge includes a smart cartridge 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.

18. The method of treating pain according to claim 18, wherein repeated sublingual administration of said dosage form to a subject results in a T_max with a coefficient of variation of less than 40%.