Sublingual films
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.
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.