Sublingual apomorphine

• US 9,044,475 B2
• Filed: 06/11/2010
• Issued: 06/02/2015
• 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): Azpuru, Carlos
• Assistant Examiner(s): Browe, David
• Application Number:
  US12/813,820
• Publication Number:
  US 20110111011A1
• Time in Patent Office: 1,817 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 sublingual formulations of apomorphine that is a mucoadhesive polymer film or a strip having a first portion including an acid addition salt of apomorphine and a second portion including a pH neutralizing agent, and methods of treating Parkinson'"'"'s disease, sexual dysfunction, and depressive disorders by administering sublingually the film or strip.

Claims

1. A pharmaceutical composition in unit dosage form formulated for sublingual administration, wherein said unit dosage form is a film or a strip having a first layer and a second layer, said first layer comprising apomorphine particles comprising an acid addition salt of apomorphine and said second layer comprising a pH neutralizing agent that is an organic base, wherein (i) said unit dosage form is not effervescent, and (ii) said unit dosage form comprises a permeation enhancer.

2. The pharmaceutical composition of claim 1, wherein said unit dosage form comprises a polysaccharide.

3. The pharmaceutical composition of claim 1, wherein said film or a strip comprises a mucoadhesive polymer selected from carboxymethylcellulose, cellulose acetate, ethylcellulose, hydroxyethylcellulose, or hydroxypropylmethylcellulose.

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

5. The pharmaceutical composition of claim 1, further comprising an antioxidant.

6. The pharmaceutical composition of claim 1, wherein said permeation enhancer is glycerol monostearate.

7. The pharmaceutical composition of claim 1, wherein said first layer comprises apomorphine particles having an effective particle size of from 1 μ

m to 10 μ

m, wherein said apomorphine particles comprise an acid addition salt of apomorphine.

8. The pharmaceutical composition of claim 7, wherein said apomorphine particles comprise apomorphine hydrochloride.

9. The pharmaceutical composition of claim 8, wherein said unit dosage form comprises from 2 to 40 mg of an acid addition salt of apomorphine.

10. The pharmaceutical composition of claim 8, wherein said unit dosage form comprises apomorphine particles in a mucoadhesive polymer.

11. The pharmaceutical composition of claim 8, further comprising a third layer positioned between the first layer and the second layer.

12. The pharmaceutical composition of claim 9, wherein said unit dosage form comprises from 12 to 30 mg of an acid addition salt of apomorphine.

13. The pharmaceutical composition of claim 9, wherein said unit dosage form comprises 12±

3 mg of an acid addition salt of apomorphine.

14. The pharmaceutical composition of claim 9, wherein said unit dosage form comprises 22±

4 mg of an acid addition salt of apomorphine.

15. The pharmaceutical composition of claim 9, wherein said unit dosage form comprises 30±

5 mg of an acid addition salt of apomorphine.

16. The pharmaceutical composition of claim 9, wherein said unit dosage form comprises 35±

5 mg of an acid addition salt of apomorphine.