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

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.