Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain
Compositions, methods and systems for administration of small volume sufentanil-containing drug dosage forms to the oral mucosa of a subject are disclosed.
1. A dosage form for oral transmucosal administration to a subject, comprising: from about 5 to about 100 micrograms (mcg) of sufentanil and a bioadhesive material, wherein; (i) said bioadhesive material provides for adherence of the dosage form to the oral mucosa of said subject during the period of drug delivery; (ii) said dosage form has a volume of less than 30 microliters or a mass of less than 30 mg; and (iii) after administration of said dosage form to said subject, said dosage form provides a minimal saliva response and minimal swallowing of sufentanil; at least 55% of drug delivery of sufentanil occurs via the oral transmucosal route; said dosage form provides a dose-normalized mean C max of 1.59-2.75 pg/mL per mcg dosed; and said dosage form provides a T max with a coefficient of variation of less than 40%.
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 dosage form according to claim 1 , wherein said dosage form has a mass of less than 10 mg or a volume of less than 10 μl.
4. The dosage form according to claim 1 , wherein said oral transmucosal administration is sublingual or buccal administration.
5. The dosage form according to claim 1 , wherein the erosion time of said dosage form is from 30 seconds up to a time selected from the group consisting of 5 minutes, 10 minutes, 15 minutes and 30 minutes.
6. The drug dosage form according to claim 4 , wherein said dosage form delivers at least 60% of the total amount of sufentanil in said dosage form via the sublingual route.
7. The drug dosage form according to claim 4 , wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 50%.
8. The dosage form according to claim 4 , wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 60%.
9. The dosage form according to claim 4 , wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 70%.
10. The drug dosage form according to claim 4 , wherein following repeated sublingual administrations 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 4 , wherein the difference between the T max following repeated sublingual administrations and the time of the previous sublingual administration is shorter than the T max following a single sublingual administration to said subject.
12. The formulation according to claim 1 , wherein said dosage form is selected from the group consisting of a lozenge, a pill, a tablet, a membrane and a strip.
13. The dosage form according to claim 12 , wherein said dosage form is a tablet.
14. A single dose applicator (SDA), comprising a dosage form according to claim 1 .
15. A method of treating pain, comprising administering the dosage form of claim 1 to a patient in need thereof using a single dose applicator (SDA).
16. The method according to claim 15 , wherein said pain is acute pain, breakthrough pain or post-operative pain.
17. The method according to claim 16 , wherein said pain is acute inpatient pain.
18. The method according to claim 16 , wherein said pain is post-operative pain.