Film formulations containing dexmedetomidine and methods of producing them
Disclosed herein is a self-supporting, dissolvable, film containing dexmedetomidine or a pharmaceutically acceptable salt thereof. The film is administered orally to treat various conditions, particularly agitation, by transmucosal delivery of the active agent.
1. A composition comprising:
(i) dexmedetomidine or a pharmaceutically acceptable salt thereof;
(ii) a first water-soluble hydroxypropyl cellulose polymer having a molecular weight of about 40,000 daltons in an amount of about 3% to about 15% w/w of the total composition weight;
(iii) a second water-soluble hydroxypropyl cellulose polymer having a molecular weight of about 140,000 daltons in an amount of about 3% to about 8% w/w of the total composition weight;
(iv) a third water-soluble hydroxypropyl cellulose polymer having a molecular weight of about 370,000 daltons in an amount of about 10% to about 50% w/w of the total composition weight; and
(v) a water-soluble polyethylene oxide polymer having a molecular weight of about 600,000 daltons in an amount of about 40% to about 70% w/w of the total composition weight.
2. The composition according to claim 1 in the form of a self-supporting, dissolvable mucoadhesive film.
3. The composition according to claim 2 , wherein the self-supporting, dissolvable mucoadhesive film is suitable for sublingual or buccal administration.
4. A composition comprising:
(a) dexmedetomidine hydrochloride; and further comprising
(b) a film substrate comprising:
(i) hydroxypropyl cellulose having a molecular weight of about 40,000 daltons in an amount of about 3% to about 15% w/w of the total composition weight;
(ii) hydroxypropyl cellulose having a molecular weight of about 140,000 daltons in an amount of about 3% to about 8% w/w of the total composition weight;
(iii) hydroxypropyl cellulose having a molecular weight of about 370,000 daltons in an amount of about 10% to about 50% w/w of the total composition weight; and
(iv) polyethylene oxide having a molecular weight of about 600,000 daltons in an amount of about 40% to about 70% w/w of the total composition weight.
5. The composition according to claim 4 , wherein dexmedetomidine hydrochloride is present at about 0,05% to about 3% w/w of the total composition weight.
6. The composition according to claim 4 , wherein dexmedetomidine hydrochloride is present at about 0.1% to about 0.2% w/w of the total composition weight, hydroxypropyl cellulose having a molecular weight of about 40,000 daltons is present at about 5% w/w of the total composition weight and hydroxypropyl cellulose having a molecular weight of about 140,000 daltons is present at about 5% w/w of the total composition weight.
7. The composition according to claim 4 , wherein the composition comprises one or more colorants.
8. The composition according to claim 2 , wherein the film has a thickness of about 20 micrometers to about 200 micrometers.
9. The composition according to claim 2 , wherein the film has a thickness of about 20 micrometers to about 200 micrometers and covers an area (width×length) of about 100 mm 2 to about 300 mm 2 .
10. The composition according to claim 2 , wherein the film has a disintegration time of about 60 seconds to about 180 seconds.
11. The composition according to claim 2 , wherein the film has a mucoadhesion force of about 1000 g to about 200 g.
12. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 10 micrograms.
13. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 20 micrograms.
14. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 30 micrograms.
15. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 40 micrograms.
16. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 60 micrograms.
17. A method of treating agitation in a subject comprising administering buccally to the agitated subject a composition according to claim 4 .
18. The composition according to claim 2 , wherein the film is completely dissolvable in oral mucosal fluid in about 1 minute to about 5 minutes.
19. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 90 micrograms.
20. The composition according to claim 4 , wherein said dexmedetomidine hydrochloride is present in an amount of about 120 micrograms.
21. The composition according to claim 4 , wherein said composition is administered in one or more units to provide a total daily dose of dexmedetomidine hydrochloride of about 120 micrograms.
22. The composition according to claim 4 , wherein said composition is administered in one or more units to provide a total daily dose of dexmedetomidine hydrochloride of about 180 micrograms.
23. The composition according to claim 3 , wherein said film is administered in one or more units to provide a total daily dose of dexmedetomidine or a pharmaceutically acceptable salt thereof of about 120 micrograms.
24. The composition according to claim 3 , wherein said film is administered in one or more units to provide a total daily dose of dexmedetomidine or a pharmaceutically acceptable salt thereof of about 180 micrograms.