Sublingual films

Patent metadata

Field	Value
Publication number	US-10285953-B2
Application number	US-201615225992-A
Country	US
Kind code	B2
Filing date	Aug 2, 2016
Priority date	Dec 16, 2010
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The invention features sublingual film formulations of dopamine agonists and methods of treating Parkinson's disease, tremors, restless leg syndrome, sexual dysfunction, and depressive disorders therewith.

First claim

What is claimed is:

1. A pharmaceutical composition in unit dosage form formulated for sublingual administration, wherein said unit dosage form is a film comprising (i) from 2 to 60 mg of an acid addition salt of apomorphine and (ii) from 10±2% to 50±5% (w/w) of a pH neutralizing agent that is an inorganic base selected from the group consisting of inorganic oxides and inorganic hydroxides, wherein said film comprises particles comprising said inorganic base; wherein said unit dosage form further comprises from 3 to 12% (w/w) of plasticizing agent; and wherein said unit dosage form comprises from 30±5% to 65±5% of said acid addition salt of apomorphine.

2. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises from 15±5% to 50±5% (w/w) of said pH neutralizing agent.

3. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises from 10±2% to 25±5% (w/w) of said pH neutralizing agent.

4. The pharmaceutical composition of claim 1 , wherein said plasticizing agent is a polyol, oleic acid, or triacetin.

5. The pharmaceutical composition of claim 4 , wherein said plasticizing agent is a polyol selected from sorbitol, mannitol, maltitol, xylitol, glycerol, propylene glycol, and polyethylene glycol.

6. The pharmaceutical composition of claim 1 , wherein said unit dosage form further comprises from 1 to 50% (w/w) of hydrolyzed starch.

7. The pharmaceutical composition of claim 6 , wherein said hydrolyzed starch is a dextrin or a maltodextrin.

8. The pharmaceutical composition of claim 1 , wherein said unit dosage form further comprises an antioxidant.

9. The pharmaceutical composition of claim 1 , wherein said unit dosage form further comprises from 0.05 to 2.5% (w/w) of metabisulfite.

10. The pharmaceutical composition of claim 1 , wherein said unit dosage form further comprises from 0.2 to 5% (w/w) of a permeation enhancer.

11. The pharmaceutical composition of claim 1 , wherein said unit dosage form further comprises from 0.2 to 5% (w/w) of glycerol monostearate.

12. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises carboxymethylcellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, or methyl cellulose.

13. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 4±1 mg of apomorphine hydrochloride.

14. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 8±2 mg of apomorphine hydrochloride.

15. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 10±3 mg of apomorphine hydrochloride.

16. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 12±3 mg of apomorphine hydrochloride.

17. The pharmaceutical composition of claim 1 , wherein the pH neutralizing agent is present in an amount such that a unit dosage form placed in 1 mL of unbuffered water at pH 7 results in a pH of between 2.5 and 8.0.

18. The pharmaceutical composition of claim 1 , wherein said acid addition salt of apomorphine is apomorphine hydrochloride.

19. The pharmaceutical composition of claim 1 , wherein said unit dosage form is a monolayer film.

20. The pharmaceutical composition of claim 1 , wherein said unit dosage form is a bilayer film.

21. The pharmaceutical composition of claim 1 , wherein said inorganic base is selected from the group consisting of aluminum hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, and sodium hydroxide.

22. A method of treating Parkinson's disease in a subject, said method comprising sublingual administration of the pharmaceutical composition of claim 1 in an amount effective to treat said subject.

Assignees

• Sunovion Pharmaceuticals Inc

Inventors

• Bryson Nathan John
• Giovinazzo Anthony John
• Barnhart Scott David
• Koons Michael Clinton

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61F13/00063 Primary

  comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic (drug delivery dressings A61K9/70; chemical aspect of the additives A61L15/00) · CPC title

• B29C66/45

  Joining of substantially the whole surface of the articles (methods or apparatus for laminating B32B37/00) · CPC title

• A61K9/006 Primary

  Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays · CPC title