R(+)-N-methyl-propargyl-aminoindan

Patent metadata

Field	Value
Publication number	US-9339469-B2
Application number	US-201213647622-A
Country	US
Kind code	B2
Filing date	Oct 9, 2012
Priority date	Oct 10, 2011
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

The subject invention provides R(+)-N-methyl-propargyl-aminoindan or a pharmaceutically acceptable salt thereof and a composition containing R(+)-N-propargyl-1(R)-aminoindan or a pharmaceutically acceptable salt thereof, and a compound of R(+)-N-methyl-propargyl-aminoindan or a salt thereof.

First claim

What is claimed is:

1. A pharmaceutical composition comprising rasagiline or a pharmaceutically acceptable salt thereof, citric acid, R(+)-N-methyl-propargyl-aminoindan or a salt thereof, and at least one pharmaceutically acceptable carrier, wherein R(+)-N-methyl-propargyl-aminoindan is present in the composition in an amount greater than about 0.03%, and not more than about 1.0%, by weight, relative to the amount of rasagiline, based on a determination by an HPLC method.

2. The pharmaceutical composition of claim 1 , wherein the amount of R(+)-N-methyl-propargyl-aminoindan is greater than about 0.1%, by weight, relative to the amount of rasagiline, based on a determination by an HPLC method.

3. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is less than one week old, and the temperature during the less than one week did not exceed ambient temperature.

4. The pharmaceutical composition of claim 1 , which comprises rasagiline as free base.

5. The pharmaceutical composition of claim 1 , which comprises the pharmaceutically acceptable salt of rasagiline, and which salt is rasagiline citrate.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a solid pharmaceutical composition.

7. The pharmaceutical composition of claim 6 which is in tablet form.

8. The pharmaceutical composition of claim 7 having a core and a coating, wherein the core of the tablet comprises an amount of rasagiline free base, citric acid and mannitol.

9. The pharmaceutical composition of claim 8 wherein in the core of the tablet the weight ratio of mannitol to citric acid is between 45 to 1 and 10 to 1.

10. The pharmaceutical composition of claim 9 wherein in the core of the tablet the weight ratio of mannitol to citric acid is between 30 to 1 and 25 to 1.

11. The pharmaceutical composition of claims 7 having a core and a coating, wherein the core of the tablet comprises an amount of rasagiline and citric acid, about 59.9% of mannitol, about 0.53% of aerosil, about 6.6% of starch NF, about 26.3% of pregelatinized starch, about 2.0% of stearic acid, and about 2.0% of talc, by weight, relative to the weight of the core of the tablet.

12. The pharmaceutical composition of claim 11 , wherein the core of the tablet comprises an amount of rasagiline and citric acid, 45.5 mg of mannitol, 0.4 mg of aerosil, 5.0 mg of starch NF, 20.0 mg of pregelatinized starch, 1.5 mg of stearic acid, 1.5 mg of talc, and the coating of the tablet comprises two coating layers, of which the inner of the two coating layers comprises 3.5 mg of hypromellose and the outer of the two coating layers comprises 4.0 mg of methacrylic acid ethyl acrylate copolymer, 0.8 mg of triethyl citrate, and 1.9 mg of talc extra fine.

13. The pharmaceutical composition of claim 8 , wherein the amount of rasagiline in the core is 0.5 mg.

14. The pharmaceutical composition of claim 7 having a core and a coating, wherein the core of the tablet comprises an amount of rasagiline and citric acid, about 59.2% of mannitol, about 0.53% of aerosil, about 6.6% of starch NF, about 26.3% of pregelatinized starch, about 2.0% of stearic acid, and about 2.0% of talc, by weight, relative to the weight of the core of the tablet.

15. The pharmaceutical composition of claim 14 , wherein the core of the tablet comprises an amount of rasagiline and citric acid, 45.0 mg of mannitol, 0.4 mg of aerosil, 5.0 mg of starch NF, 20.0 mg of pregelatinized starch, 1.5 mg of stearic acid, 1.5 mg of talc, and the coating of the tablet comprises two coating layers, of which the inner of the two coating layers comprises 3.5 mg of hypromellose and the outer of the two coating layers comprises 4.0 mg of methacrylic acid ethyl acrylate copolymer, 0.8 mg of triethyl citrate, and 1.9 mg of talc extra fine.

16. The pharmaceutical composition of claim 8 , wherein the amount of rasagiline in the core is 1.0 mg.

17. The pharmaceutical composition of claim 1 , wherein not more than 1.0% by weight of rasagiline citramide or a salt thereof is present in the pharmaceutical composition relative to the amount of rasagiline.

18. A process for preparing a pharmaceutical composition comprising rasagiline or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, comprising:
a) obtaining a batch of rasagiline or a pharmaceutically acceptable salt thereof;
b) analyzing the batch for the presence of the compound recited by claim 1 by a suitable apparatus; and
c) preparing the pharmaceutical composition from the batch only if the amount of the compound is not more than about 1.0% by weight relative to the amount of rasagiline.

19. A process for preparing a packaged pharmaceutical composition comprising rasagiline or a pharmaceutically acceptable salt thereof comprising:
a) obtaining a pharmaceutical composition of rasagiline or a pharmaceutically acceptable salt thereof;
b) analyzing the pharmaceutical composition for the presence of the compound recited by claim 1 by a suitable apparatus; and
c) packaging the pharmaceutical composition only if the amount of the compound is not more than about 1.0% by weight relative to the amount of rasagiline.

20. A process of distributing a validated batch of a pharmaceutical composition comprising rasagiline or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, comprising:
a) obtaining a batch of the pharmaceutical composition;
b) performing stability testing with a sample of the batch;
c) determining the total amount of the compound recited by claim 1 in the sample of the batch by a suitable apparatus after stability testing;
d) validating the batch for distribution only if the sample of the batch after stability testing is determined to have not more than about 1.0% by weight of the compound relative to the amount of rasagiline; and
e) distributing the validated batch.

21. A method for treating Parkinson's disease in a patient comprising administering to the patient an amount of the pharmaceutical composition of claim 1 effective to treat Parkinson's disease in the patient.

Assignees

• Teva Pharma

Inventors

• Safadi Muhammad
• Frenkel Anton
• Keisar Michal
• Licht Danit
• Bahar Eliezer
• Lidor-Hadas Ramy
• Zholkovsky Marina
• Cohen Rachel

Classifications

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K9/2846

  Poly(meth)acrylates · CPC title

• A61K9/2886

  having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209) · CPC title

• A61K9/2059

  Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin · CPC title