Sublingual apomorphine

Patent metadata

Field	Value
Publication number	US-9669018-B2
Application number	US-201514963835-A
Country	US
Kind code	B2
Filing date	Dec 9, 2015
Priority date	Jun 12, 2009
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

Disclosed are methods of preparing a pharmaceutical composition that is a mucoadhesive film by: (i) combining a film-forming mucoadhesive polymer, apomorphine particles containing an acid addition salt of apomorphine, and a solvent to form a mixture; and (ii) pouring the mixture onto a surface and evaporating some of the solvent to form an intermediate film including the apomorphine particles; where the method further includes contacting or impregnating the intermediate film or mixture with a pH neutralizing agent to produce the mucoadhesive film containing the apomorphine particles and the pH neutralizing agent.

First claim

What is claimed is:

1. A method of preparing a pharmaceutical composition that is a mucoadhesive film comprising the steps of:
(i) combining a film-forming mucoadhesive polymer, apomorphine particles comprising an acid addition salt of apomorphine, and a solvent to form a mixture; and
(ii) pouring the mixture onto a surface and evaporating some of said solvent to form a first film comprising said apomorphine particles;
wherein said method further comprises contacting or impregnating said first film or mixture with a pH neutralizing agent to produce said mucoadhesive film, said mucoadhesive film comprising said apomorphine particles and said pH neutralizing agent.

2. The method of claim 1 , wherein said pH neutralizing agent is an inorganic base.

3. The method of claim 2 , wherein said inorganic base is sodium phosphate monobasic, sodium phosphate dibasic, sodium phosphate tribasic, potassium phosphate monobasic, potassium phosphate dibasic, potassium phosphate tribasic, or a mixture thereof.

4. The method of claim 1 , wherein said acid addition salt of apomorphine is apomorphine hydrochloride.

5. The method of claim 1 , wherein said combining further comprises adding an antioxidant.

6. The method of claim 5 , wherein said antioxidant is selected from the group consisting thiols, sulphoximines, metal chelators, sodium metabisulfite, vitamins, phenols, benzoates, uric acid, mannose, propyl gallate, selenium, stilbenes, and combinations thereof.

7. The method of claim 6 , wherein said antioxidant is sodium metabisulfite.

8. The method claim 6 , wherein said antioxidant is a metal chelator.

9. The method of claim 8 , wherein said metal chelator is EDTA.

10. The method of claim 1 , wherein said combining further comprises adding a plasticizer selected from the group consisting of glycerol, propylene glycol, fatty acid esters, sorbitan esters, citric acid esters, PEG 400, polyvinyl methyl ether, triacetin, mannitol, xylitol, and sorbitol.

11. The method of claim 10 , wherein said plasticizer is glycerol.

12. The method of claim 1 , wherein said mucoadhesive film comprises from 2 to 40 mg of said acid addition salt of apomorphine.

13. The method of claim 12 , wherein said mucoadhesive film comprises 10±3 mg said acid addition salt of apomorphine.

14. The method of claim 12 , wherein said mucoadhesive film comprises 5±3 mg of said acid addition salt of apomorphine.

15. The method of claim 12 , wherein said mucoadhesive film comprises 22±4 mg of said acid addition salt of apomorphine.

16. The method of claim 12 , wherein said mucoadhesive film comprises 27±4 mg of said acid addition salt of apomorphine.

17. The method of claim 12 , wherein said mucoadhesive film comprises 30±5 mg of said acid addition salt of apomorphine.

18. The method of claim 12 , herein said mucoadhesive film comprises 35±5 mg of said acid addition salt of apomorphine.

19. The method of claim 1 , wherein said pH neutralizing agent is an organic base.

20. The method of claim 1 , wherein said mucoadhesive film comprises a first portion comprising apomorphine particles comprising said acid addition salt of apomorphine and a second portion comprising said pH neutralizing agent, and wherein said method comprises contacting said first film with said pH neutralizing agent to produce said mucoadhesive film.

21. The method of claim 20 , wherein said first portion is a first layer, and said second portion is a second layer.

22. The method of claim 1 , wherein said mucoadhesive film is a non-effervescent, mucoadhesive film.

23. The method of claim 1 , wherein said mucoadhesive film produces an average circulating apomorphine plasma concentration of at least 3 ng/mL within 20 minutes following sublingual administration.

24. The method of claim 1 , wherein said mucoadhesive film further comprises a permeation enhancer.

25. The method of claim 1 , wherein said mucoadhesive film further comprises glycerol monostearate.

26. The method of claim 1 , wherein the film comprises 12 to 30 mg of an acid addition salt of apomorphine.

27. The method of claim 26 , wherein said acid addition salt of apomorphine is apomorphine hydrochloride.

28. The method of claim 20 , wherein the film comprise 12 to 30 mg of an acid addition salt of apomorphine.

29. The method of claim 28 , wherein said acid addition salt of apomorphine is apomorphine hydrochloride.

Assignees

• Sunovion Pharmaceuticals Inc

Inventors

• Giovinazzo Anthony John
• Hedden David Bruce
• De Somer Marc L
• Bryson Nathan John

Classifications

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P15/10

  for impotence · CPC title

• A61K9/7007

  Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence) · CPC title

• A61K9/70 Primary

  Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)} · CPC title

• A61K9/0056 Primary

  Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals · CPC title