Claims for Patent: 10,792,246

Summary for Patent: 10,792,246

Title:	Film formulations containing dexmedetomidine and methods of producing them
Abstract:	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.
Inventor(s):	Kakumanu; Vasukumar (Guntur, IN), Hanley; David Christian (Brookfield, CT), Yocca; Frank (Clinton, CT), Lathia; Chetan Dalpatbhai (Woodbridge, CT), Barnhart; Scott David (Glen Rock, PA)
Assignee:	BIOXCEL THERAPEUTICS, INC. (New Haven, CT) ARX, LLC (Glen Rock, PA)
Application Number:	16/453,679
Patent Claims:	1. A self-supporting, dissolvable, mucoadhesive film for sublingual administration 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; (iii) a second water-soluble hydroxypropyl cellulose polymer having a molecular weight of about 140,000 daltons; (iv) a third water-soluble hydroxypropyl cellulose polymer having a molecular weight of about 370,000 daltons; and (v) a water-soluble polyethylene oxide polymer having a molecular weight of about 600,000 daltons; wherein: the only polymers present in the film are water-soluble hydroxypropyl cellulose and water-soluble polyethylene oxide polymers; said first water-soluble hydroxypropyl cellulose polymer having a molecular weight of about 40,000 daltons is present at about 3% to about 8% w/w of the total film weight; said second hydroxypropyl cellulose polymer having a molecular weight of about 140,000 daltons is present at about 3% to about 8% w/w of the total film weight and said third water-soluble hydroxypropyl cellulose polymers having a molecular weight of about 370,000 daltons is present at about 20% to about 40% w/w of the total film weight; said water-soluble polyethylene oxide polymer having a molecular weight of about 600,000 daltons is present at about 50% to about 60% w/w of the total film weight; the polymers in (ii), (iii), (iv) and (v) above together form a single layer film substrate; and dexmedetomidine or a pharmaceutically acceptable salt thereof is present on one surface of said single layer film substrate. 2. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is dexmedetomidine hydrochloride which is present at a weight ratio of about 0.05 mcg to about 3 mcg for each 100 mcg of total weight of film. 3. A self-supporting, dissolvable, mucoadhesive film for sublingual administration consisting of: (a) a composition comprising: (i) dexmedetomidine hydrochloride; (ii) hydroxypropyl cellulose having a molecular weight of about 40,000 daltons; and (iii) hydroxypropyl cellulose having a molecular weight of about 140,000 daltons; and (b) a film substrate comprising: (i) hydroxypropyl cellulose having a molecular weight of about 40,000 daltons; (ii) hydroxypropyl cellulose having a molecular weight of about 140,000 daltons; (iii) hydroxypropyl cellulose having a molecular weight of about 370,000 daltons; and (iv) polyethylene oxide having a molecular weight of about 600,000 daltons; wherein the only polymers present in the film are water-soluble hydroxypropyl cellulose and water-soluble polyethylene oxide polymers; hydroxypropyl cellulose having a molecular weight of about 40,000 daltons is present at about 3% to about 8% w/w of the total film weight hydroxypropyl cellulose having a molecular weight of about 140,000 daltons is present at about 3% to about 8% w/w of the total film weight hydroxypropyl cellulose having a molecular weight of about 370,000 daltons is present at about 20% to about 40% w/w of the total film weight and polyethylene oxide having a molecular weight of about 600,000 daltons is present at about 50% to about 60% w/w of the total film weight; and the composition of part (a) is present on the surface of the film substrate (b). 4. The film according to claim 3, wherein the composition of part (a) constitutes about 0.1% to about 10% w/w of the total film weight. 5. The film according to claim 3, wherein dexmedetomidine hydrochloride is present at about 0.05% to about 3% w/w of the total film weight. 6. The film according to claim 3, wherein dexmedetomidine hydrochloride is present at about 0.1% to about 0.2% w/w of the total film weight, hydroxypropyl cellulose having a molecular weight of about 40,000 daltons is present at about 5% w/w of the total film weight and hydroxypropyl cellulose having a molecular weight of about 140,000 daltons is present at about 5% w/w of the total film weight. 7. The film according to claim 3, wherein the composition of part (a) comprises a colorant and the film substrate of part (b) comprises a colorant, wherein the colorant in part (a) is a different color from the colorant in part (b). 8. The film according to claim 3, wherein the composition of part (a) covers a portion of the surface of the film substrate of part (b). 9. The film according to claim 1, wherein the film has a thickness of about 20 micrometers to about 200 micrometers. 10. The film according to claim 1, wherein the film has a thickness of about 20 micrometers to about 200 micrometers and covers an area (width.times.length) of about 100 mm.sup.2 to about 300 mm.sup.2. 11. The film according to claim 1, wherein the film has a disintegration time of about -14 60 seconds to about 180 seconds. 12. The film according to claim 1, wherein the film has a mucoadhesion force of about 1000 g to about 2000 g. 13. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is present in an amount of about 10 micrograms. 14. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is present in an amount of about 20 micrograms. 15. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is present in an amount of about 4-0 micrograms. 16. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is present in an amount of about 60 micrograms. 17. A method of treating agitation comprising administering sublingually to the agitated subject a film according to claim 1. 18. The film according to claim 1, wherein the film is completely dissolvable in oral mucosal fluid in about 1 minute to about 5 minutes. 19. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is present in an amount of about 90 micrograms. 20. The film according to claim 1, wherein said dexmedetomidine or a pharmaceutically acceptable salt thereof is present in an amount of about 120 micrograms. 21. The film according to claim 1, 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. 22. The film according to claim 1, 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. 23. The film 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 film 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. 25. The film according to claim 1, wherein dexmedetomidine or a pharmaceutically acceptable salt thereof is present on one surface of said film substrate and covers a portion of the surface of said film substrate at more than one isolated surface locations. 26. The film according to claim 3, wherein said composition of part (a) is present on the surface of the film substrate (h) and covers a portion of the surface of said film substrate at more than one isolated surface locations.