Sublingual apomorphine
The invention features methods involving the use of sublingual film formulations of apomorphine for treating Parkinson's disease. The methods involve providing the sublingual film formulation and administering the sublingual film formulation sublingually in the mouth of a subject by contacting sublingual mucosal tissue with the film.
1. A method of treating Parkinson's disease in a subject in need thereof, the method comprising:
(i) providing a pharmaceutical composition in unit dosage form that is a film having a first layer comprising apomorphine particles comprising an acid addition salt of apomorphine and a second layer comprising a pH neutralizing agent, wherein the film is a non-effervescent, mucoadhesive film comprising a mucoadhesive polymer and wherein the film comprises the acid addition salt of apomorphine in an amount effective to treat Parkinson's disease; and
(ii) administering the film by placing the film sublingually in the mouth of the subject and contacting sublingual mucosal tissue with the film.
2. The method of claim 1 , wherein the acid addition salt of apomorphine is apomorphine hydrochloride.
3. The method of claim 1 , wherein the film further comprises an antioxidant.
4. The method of claim 1 , wherein the film further comprises a permeation enhancer.
5. The method of claim 4 , wherein the permeation enhancer is glycerol monostearate.
6. The method of claim 1 , wherein the first layer comprises apomorphine particles having an effective particle size of from 1 μm to 10 μm.
7. The method of claim 1 , wherein the film comprises a polysaccharide.
8. The method of claim 1 , wherein the film comprises from 2 to 40 mg of an acid addition salt of apomorphine.
9. The method of claim 8 , wherein the film comprises from 12 to 30 mg of an acid addition salt of apomorphine.
10. The method of claim 8 , wherein the film comprises 12±3 mg of an acid addition salt of apomorphine.
11. The method of claim 8 , wherein the film comprises 22±4 mg of an acid addition salt of apomorphine.
12. The method of claim 8 , wherein the film comprises 30±5 mg of an acid addition salt of apomorphine.
13. The method of claim 8 , wherein the film comprises 35±5 mg of an acid addition salt of apomorphine.
14. The method of claim 1 , wherein the pH neutralizing agent is an organic base.
15. The method of claim 1 , wherein following sublingual administration the film produces an average circulating apomorphine plasma concentration of at least 3 ng/mL within 20 minutes.
16. The method of claim 1 , further comprising a third layer positioned between the first layer and the second layer.