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 a first layer and a second layer, wherein the first layer comprises from 2 to 60 mg of apomorphine hydrochloride and wherein the second layer comprises 25±5% to 65±5% (w/w) pyridoxine.
2. The pharmaceutical composition of claim 1 , wherein said film further comprises from 3 to 12% (w/w) plasticizing agent.
3. The pharmaceutical composition of claim 2 , wherein said plasticizing agent is a polyol, oleic acid, or triacetin.
4. The pharmaceutical composition of claim 3 , wherein said plasticizing agent is a polyol selected from sorbitol, mannitol, maltitol, xylitol, glycerol, propylene glycol, and polyethylene glycol.
5. The pharmaceutical composition of claim 1 , wherein said film comprises from 1 to 50% (w/w) hydrolyzed starch.
6. The pharmaceutical composition of claim 5 , wherein said hydrolyzed starch is a dextrin or a maltodextrin.
7. The pharmaceutical composition of claim 1 , wherein said film further comprises an antioxidant.
8. The pharmaceutical composition of claim 7 , wherein said film further comprises from 0.05 to 2.5% (w/w) metabisulfite.
9. The pharmaceutical composition of claim 1 , wherein said film further comprises from 0.2 to 5% (w/w) of a permeation enhancer.
10. The pharmaceutical composition of claim 9 , wherein said permeation enhancer is glycerol monostearate.
11. The pharmaceutical composition of claim 1 , wherein said film comprises carboxymethylcellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, or methyl cellulose.
12. The pharmaceutical composition of claim 1 , wherein following sublingual administration to a subject said unit dosage form produces an average circulating concentration of at east 3 ng/mL within a period of from 5 to 15 minutes.
13. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 12±3 mg of apomorphine hydrochloride.
14. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 22±4 mg of apomorphine hydrochloride.
15. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 30±5 mg of apomorphine hydrochloride.
16. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises 35±5 mg of apomorphine hydrochloride.
17. A method of treating Parkinson's disease in a subject, said method comprising sublingual administration of a pharmaceutical composition of claim 1 in an amount effective to treat said subject.
18. The pharmaceutical composition of claim 1 , wherein the second layer comprises 65±5% (w/w) of a pH neutralizing agent that is pyridoxine.
19. The pharmaceutical composition of claim 1 , wherein the pyridoxine 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.