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

• US 10,245,228 B2
• Filed: 07/20/2017
• Issued: 04/02/2019
• 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.
• Primary Examiner(s): Packard, Benjamin J
• Application Number:
  US15/655,316
• Publication Number:
  US 20180161270A1
• Time in Patent Office: 621 Days
• 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 oral transmucosal administration to a subject, comprising:

from 5.0 micrograms to 100 micrograms sufentanil, wherein said dosage form is bioadhesive and has a volume of less than 30 microliters or a mass of less than 30 mg, wherein the administration of the dosage form to the subject provides a Tmax with a coefficient of variation less than 40%.

2. The dosage form of claim 1, wherein the dosage form has a volume of less than 10 microliters or a mass of less than 10 mg.

3. The dosage form of claim 1, wherein after administration of the dosage form to the subject, at least 50% of the drug delivery of sufentanil occurs via the oral transmucosal route.

4. The dosage form of claim 3, wherein after administration of the dosage form to the subject, at least 55% of the drug delivery of sufentanil occurs via the oral transmucosal route.

5. The dosage form of claim 3, wherein after administration of the dosage form to the subject, at least 60% of the drug delivery of sufentanil occurs via the oral transmucosal route.

6. The dosage form of claim 1, wherein after administration of the dosage form to the subject, the dosage form provides a T_max of from about 19.8 minutes to about 60 minutes.

7. The dosage form of claim 1, wherein after administration of the dosage form to the subject results in a dose-normalized C_max of about 2.72+/−

0.84 pg/mL per mcg dosed.

8. The dosage form of claim 1, wherein after administration of the dosage form to the subject, the dosage form provides a T_max of from about 19.8 minutes to about 60 minutes and a dose-normalized C_max of about 2.72+/−

0.84 pg/mL per mcg dosed.

9. The dosage form of claim 8, wherein the transmucosal administration is to the sublingual membrane.

10. The dosage form of claim 8, wherein the administration is to the buccal membrane.

11. The dosage form of claim 1, wherein a single oral transmucosal administration of the dosage form to the subject results in a bioavailability of greater than 65%.

12. The dosage form of claim 1, wherein a single oral transmucosal administration of the dosage form to the subject results in a bioavailability of greater than 75%.

13. The dosage form of claim 1, wherein a single oral transmucosal administration of the dosage form to the subject results in a bioavailability of greater than 80%.

14. The dosage form of claim 1, wherein sufentanil is sufentanil citrate.

15. A drug delivery device comprising the dosage form of claim 1.

16. A method of treating pain in a subject, comprising administering a dosage form to the oral mucosa of a subject, wherein said dosage form is bioadhesive and comprises 5.0 micrograms to 100 micrograms, sufentanil, wherein said dosage form is bioadhesive and has a volume of less than 30 microliters or a mass of less than 30 mg.

17. The method of claim 16, wherein the dosage form has a volume of less than 10 microliters or a mass of less than 10 mg.

18. The method of claim 16, wherein the administration of the dosage form to the subject provides a T_max with a coefficient of variation less than 40%.

19. The method of claim 16, wherein after administration of the dosage form to the subject, the dosage form provides a T_max of from about 19.8 minutes to about 60 minutes.

20. The method of claim 16, wherein after administration of the dosage form to the subject, at least 50% of the drug delivery of sufentanil occurs via the oral transmucosal route.

21. The method of claim 16, wherein after administration of the dosage form to the subject, at least 55% of the drug delivery of sufentanil occurs via the oral transmucosal route.

22. The method of claim 16, wherein after administration of the dosage form to the subject, at least 60% of the drug delivery of sufentanil occurs via the oral transmucosal route.