COMPOSITIONS AND METHODS FOR PROCEDURAL SEDATION AND ANALGESIA USING ORAL TRANSMUCOSAL DOSAGE FORMS

• US 20090048237A1
• Filed: 08/07/2008
• Published: 02/19/2009
• Est. Priority Date: 08/07/2007
• Status: Abandoned Application

• Current Assignee: AcelRx Pharmaceuticals Incorporated
• Original Assignee: AcelRx Pharmaceuticals Incorporated
• Inventors: Tzannis, Stelios, Schreck, Thomas, Palmer, Pamela
• Application Number:
  US12/187,937
• Publication Number:
  US 20090048237A1
• Time in Patent Office: Days
• US Class Current: 514/218
• CPC Class Codes: A61J 7/0053 Syringes, pipettes or oral dispensers
• CPC Class Codes: A61J 7/0061 Swallow helping devices, e.g. tongue shields
• CPC Class Codes: A61J 7/0076 Medicament distribution means with pill counting devices A61J7/02; with time indication A61J7/04; containers or packages with special means for dispensing contents B65D83/00
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/5517 condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B65D 25/2811 Vertical, e.g. U-shaped
• CPC Class Codes: B65D 83/0409 the dispensing means being adapted for delivering one article, or a single dose, upon each actuation B65D83/0445 takes precedence
• CPC Class Codes: B65D 83/0847 through an aperture at the junction of two walls

Abstract

Dosage forms for procedural sedation and analgesia comprising the combination of an opioid such as sufentanil and a benzodiazepine such as triazolam for administration via the oral transmucosal route and methods for using the same are provided.

Claims

1. A solid dosage form for oral transmucosal administration to an alert, awake subject:

comprising the combination of sufentanil and triazolam, wherein following oral transmucosal administration, said subject is sedated.

2. The solid dosage form according to claim 1, wherein said dosage form has a mass selected from the group consisting of less than 100 mg, 90 mg, 80 mg, 70 mg, 60 mg, 50 mg, 40 mg, 30 mg, 29 mg, 28 mg, 27 mg, 26 mg, 25 mg, 24 mg, 23 mg, 22 mg, 21 mg, 20 mg, 19 mg, 18 mg, 17 mg, 16 mg, 15 mg, 14 mg, 13 mg, 12 mg, 11 mg, 10 mg, 9 mg, 8 mg, 7 mg, 6 mg and 5 mg.

3. The solid dosage form according to claim 2, wherein said dosage form comprises from about 5 micrograms (mcg) to about 50 mcg of sufentanil.

4. The solid dosage form according to claim 2, wherein said dosage form comprises from about 100 mcg to about 500 mcg of triazolam.

5. The solid dosage form according to claim 3, wherein said dosage form comprises from about 100 mcg to about 500 mcg of triazolam.

6. The drug dosage form according to claim 5, wherein oral transmucosal administration of said dosage form to a subject results in a T_max for sufentanil with an overall average coefficient of variation of less than 40%.

7. The drug dosage form according to claim 1, wherein said oral transmucosal administration is sublingual administration.

8. The drug dosage form according to claim 5, wherein said oral transmucosal administration is sublingual administration.

9. The solid dosage form according to claim 1, wherein following administration to said subject, the total area under the RASS sedation curve (AUC_total) is greater when the combination of sufentanil and triazolam is administered to the subject as compared to administration of an equivalent dose of sufentanil alone.

10. The solid dosage form according to claim 5 wherein following administration to said subject the total area under the curve (AUC_total) is greater when the combination of sufentanil and triazolam is administered to the subject as compared to administration of an equivalent dose of sufentanil alone.

11. The solid dosage form according to claim 5, wherein following administration to said subject, the mean T_max for sufentanil is substantially the same when the combination of sufentanil and triazolam is administered to the subject as compared to administration of an equivalent dose of sufentanil alone.

12. The solid dosage form according to claim 5, wherein following administration to said subject, the mean C_max for sufentanil is substantially the same when the combination of sufentanil and triazolam is administered to the subject as compared to administration of an equivalent dose of sufentanil alone.

13. The solid dosage form according to claim 5, wherein following administration to said subject, onset of sedation is evident in less than one hour.

14. The solid dosage form according to claim 5, wherein following administration the duration of sedation is 4 hours or less.

15. The drug dosage form according to claim 5, wherein oral transmucosal administration of said dosage form to a subject results in a relative AUC_0-last for sufentanil of greater than 60%.

16. The drug dosage form according to claim 5, wherein oral transmucosal administration of said dosage form to a subject results in a relative AUC_0-last for sufentanil of greater than 70%.

17. The drug dosage form according to claim 5, wherein oral transmucosal administration of said dosage form to a subject results in a relative AUC_0-last for sufentanil of greater than 80%.

18. The drug dosage form according to claim 5, wherein oral transmucosal administration of said dosage form to a subject results in a relative AUC_0-last for sufentanil with a coefficient of variation of less than 40%.

19. The solid dosage form according to claim 5, comprising an amount of sufentanil effective to induce sedation, but below a dose that induces respiratory depression.

20. A single dose applicator (SDA), comprising a dosage form according to claim 5.

21. A single dose applicator (SDA), comprising a dosage form according to claim 8.

22. A single dose applicator (SDA), comprising a dosage form according to claim 12.

23. A method for procedural sedation of a subject, comprising administering a dosage form according to claim 1 to a subject, wherein following administration of said dosage form to a subject, said subject is sedated.

24. A method for procedural sedation of a subject, comprising administering a dosage form according to claim 5 to an alert, awake subject, wherein following administration said subject is sedated.

25. The method according to claim 24, wherein said dosage form has a mass selected from the group consisting of less than 100 mg, 90 mg, 80 mg, 70 mg, 60 mg, 50 mg, 40 mg, 30 mg, 29 mg, 28 mg, 27 mg, 26 mg, 25 mg, 24 mg, 23 mg, 22 mg, 21 mg, 20 mg, 19 mg, 18 mg, 17 mg, 16 mg, 15 mg, 14 mg, 13 mg, 12 mg, 11 mg, 10 mg, 9 mg, 8 mg, 7 mg, 6 mg and 5 mg.

26. The method according to claim 24, wherein said dosage form comprises from about 5 micrograms (mcg) to about 50 mcg of sufentanil.

27. The method according to claim 24, wherein said dosage form comprises from about 100 mcg to about 500 mcg of triazolam.

28. The method according to claim 26, wherein said dosage form comprises from about 100 mcg to about 500 mcg of triazolam.

29. A method for procedural sedation of a subject, comprising administering a dosage form according to claim 5 to a subject, wherein administration of said dosage form to a subject results in a relative AUC_0-last of sufentanil of greater than 60%.

30. A method for procedural sedation of a subject, comprising administering a dosage form according to claim 5 to a subject, wherein administration of said dosage form to a subject results in a relative AUC_0-last of sufentanil of greater than 70%.

31. A method for procedural sedation of a subject, comprising administering a dosage form according to claim 5 to a subject, wherein administration of said dosage form to a subject results in a relative AUC_0-last of sufentanil of greater than 80%.

32. The method according to claim 28, wherein oral transmucosal administration of said dosage form to a subject results in a T_max for sufentanil with an overall average coefficient of variation of less than 40%.

33. The method according to claim 28, wherein following administration to said subject, the mean T_max for sufentanil is substantially the same as when the equivalent dose of sufentanil is administered in the absence of triazolam.

34. The method according to claim 28, wherein following administration to said subject, the mean C_max for sufentanil is substantially the same as when the equivalent dose of sufentanil is administered in the absence of triazolam.

35. The method according to claim 28, wherein said oral transmucosal administration is sublingual administration.

36. The method according to claim 28, wherein following administration to said subject sedation the total area under the curve (AUC_total) is greater when the combination of sufentanil and triazolam is administered to the subject as compared to administration of an equivalent dose of sufentanil alone.

37. The method according to claim 28, wherein following administration to said subject, a first onset of sedation is evident in less than one hour.

38. The method according to claim 28, wherein following administration the duration of sedation is 4 hours or less.

39. A method for procedural sedation of a subject, comprising, administering a dosage form according to claim 5 to a subject using a handheld dispensing device for placement of said dosage form in the sublingual space.

40. The method according to claim 39, wherein said a handheld dispensing device is a single dose applicator (SDA).