Sublingual apomorphine

• US 9,326,981 B2
• Filed: 04/10/2015
• Issued: 05/03/2016
• Est. Priority Date: 06/12/2009
• Status: Active Grant

• Current Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Original Assignee: Cynapsus Therapeutics Inc. (Sumitomo Pharma America, Inc.)
• Inventors: Giovinazzo, Anthony John, Hedden, David Bruce, Bryson, Nathan John, De Somer, Marc L.
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Browe, David
• Application Number:
  US14/684,146
• Publication Number:
  US 20150216859A1
• Time in Patent Office: 389 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/0056 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 Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

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.

Claims

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 μ

m to 10 μ

m.

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.