Bioadhesive drug formulations for oral transmucosal delivery
Bioadhesive drug formulations that adhere to an oral mucosal membrane of a subject are provided together with single dose applicators and devices for delivering the drug formulations to the oral mucosa, and methods for using the same.
1. A bioadhesive tablet for sublingual administration to a subject, comprising:
(a) from about 2.5 to about 100 micrograms of sufentanil, expressed as the base; and
(b) a bioadhesive material, wherein said bioadhesive material is present at 2-30% by weight and provides for adherence to the oral mucosa of said subject, and said tablet has a volume of from about 0.1 microliters to about 50 microliters, wherein after administration of said tablet to said subject, said tablet provides a minimal saliva response and minimal swallowing of sufentanil; and at least 55% of drug delivery of sufentanil occurs via the oral transmucosal route.
2. The tablet according to claim 1 , wherein said tablet becomes a hydrogel upon contact with an aqueous fluid.
3. The tablet according to claim 1 , wherein said tablet is an eroding tablet wherein upon contact with an aqueous fluid, the surface of the tablet hydrates and erodes, without formation of a hydrogel.
4. The tablet according to claim 1 , wherein upon contact with an aqueous fluid said tablet disintegrates and forms a film.
5. The tablet according to claim 1 , wherein dissolution of said tablet is independent of pH.
6. The tablet according to claim 5 , wherein dissolution of said tablet is independent of pH over a pH range of about 4 to 8.
7. A single dose applicator (SDA) comprising a tablet according to claim 1 , wherein said SDA is a syringe.
8. A drug dispensing device comprising the tablet according to claim 1 , wherein said drug dispensing device is effective to check user identification and provide a lockout period between dose dispenses.
9. The tablet according to claim 1 , wherein said tablet has a volume of from about 0.5 to about 10.0 microliters.
10. The tablet according to claim 1 , wherein said tablet has a volume of from about 1.0 to about 25 microliters.
11. The tablet according to claim 1 , wherein said tablet has a volume of from about 3.0 to about 15.0 microliters.
12. The tablet according to claim 1 , wherein said tablet comprises 10 micrograms of sufentanil, expressed as the base.
13. The tablet according to claim 1 , wherein said tablet comprises 15 micrograms of sufentanil, expressed as the base.
14. The tablet according to claim 1 , wherein said tablet has a thickness of from 0.5 to 3.0 mm.
15. The tablet according to claim 1 , wherein said tablet disintegrates over a period of 10-30 minutes following sublingual administration to said subject.
16. The tablet according to claim 1 , wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 70%.
17. The tablet according to claim 1 , wherein said tablet further comprises one or more excipients that affect both tablet disintegration kinetics and drug release from said tablet.
18. The tablet according to claim 17 , wherein said one or more excipients that affect tablet disintegration kinetics and drug release from said tablet is crosslinked sodium carboxy methylcellulose.
19. The tablet according to claim 1 , wherein following administration, said tablet adheres to the oral mucosa of said subject throughout the period of drug delivery.
20. The tablet according to claim 17 , wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 70%.
21. The SDA according to claim 7 , wherein said SDA is effective to accurately place said tablet in the sublingual space.
22. The SDA according to claim 21 , wherein said tablet remains dry in said SDA prior to dispensing, at which point a single tablet is dispensed from the SDA into the mouth of said subject.
23. The drug dispensing device according to claim 8 , wherein said drug dispensing device is effective to accurately place said tablet in the sublingual area.
24. The drug dispensing device according to claim 23 , wherein said tablet remains dry in the drug dispensing device prior to dispensing, at which point a single tablet is dispensed from the drug dispensing device into the mouth of said subject.
25. The drug dispensing device according to claim 23 , wherein said drug dispensing device further comprises a user interface wherein dosage history can be transferred to another device, computer or network.
26. The bioadhesive tablet according to claim 1 , wherein said tablet exhibits an attachment force of from 0.03 to 0.18 N/cm 2 to a porcine mucosa substrate in vitro.