Methods of producing anamorelin hydrochloride having controlled chloride content

Patent metadata

Field	Value
Publication number	US-9872883-B2
Application number	US-201615135147-A
Country	US
Kind code	B2
Filing date	Apr 21, 2016
Priority date	Apr 20, 2012
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

The present invention relates to particulate forms of anamorelin monohydrochloride or a composition comprising anamorelin monohydrochloride having controlled chloride content, preferably isolated in an amorphous and/or fine particulate state, processes for making the particulate forms, and pharmaceutical compositions comprising the particulate forms.

First claim

The invention claimed is:

1. A method of making a pharmaceutical dosage form comprising:
a) combining a therapeutically effective amount of anamorelin monohydrochloride with one or more pharmaceutically acceptable excipients to form a mixture;
b) processing said mixture into a finished dosage form; and
c) repeating steps (a) and (b) one or more additional times using anamorelin monohydrochloride from different batches, wherein the different batches comprise from 5.8% to 6.2% chloride.

2. The method of claim 1 , wherein the different batches comprise from 5.9% to 6.1% chloride.

3. The method of claim 1 wherein the anamorelin monohydrochloride comprises less than 3% total impurities selected from by-products, contaminants, and degradation products.

4. The method of claim 1 wherein the anamorelin monohydrochloride comprises less than 2% total impurities selected from by-products, contaminants, and degradation products.

5. The method of claim 1 wherein the anamorelin monohydrochloride comprises less than 1% total impurities selected from by-products, contaminants, and degradation products.

6. The method of claim 1 wherein the anamorelin monohydrochloride comprises less than 5% water.

7. The method of claim 1 wherein the anamorelin monohydrochloride comprises less than 3% water.

8. The method of claim 1 wherein the anamorelin monohydrochloride comprises less than 2% water.

9. The method of claim 1 wherein the anamorelin monohydrochloride is in an isolated state.

10. The method of claim 1 wherein the finished dosage form is a tablet or capsule or pellets or granules or powders.

11. The method of claim 1 wherein the anamorelin monohydrochloride has a solubility in water greater than 100 mg/mL.

12. The method of claim 1 wherein the anamorelin monohydrochloride has a solubility in water greater than 333 mg/mL.

13. The method of claim 1 wherein the anamorelin monohydrochloride has a stability defined by a percentage increase in impurities of no more than 114% when stored at 25° C. and a relative humidity of 60% for two years.

14. The method of claim 2 wherein the anamorelin monohydrochloride has a stability defined by a percentage increase in impurities of no more than 48% when stored at 25° C. and a relative humidity of 60% for two years.

15. The method of claim 1 wherein the anamorelin monohydrochloride has a chloride content of from 6.0-6.1%.

16. The method of claim 1 wherein the anamorelin monohydrochloride has a residual solvent concentration less than 5000 ppm, wherein the residual solvent concentration excludes water.

17. The method of claim 1 wherein the anamorelin monohydrochloride has a solubility in water greater than 333 mg/mL, and a stability defined by a percentage increase in impurities of no more than 114% when stored at 25° C. and a relative humidity of 60% for two years.

18. The method of claim 1 wherein the anamorelin monohydrochloride has a residual solvent concentration excluding water less than 5000 ppm, a solubility in water greater than 333 mg/mL, and a stability defined by a percentage increase in impurities of no more than 114% when stored at 25° C. and a relative humidity of 60% for two years.

19. A pharmaceutical dosage form made by the process of claim 1 .

20. A pharmaceutical dosage form made by the process of claim 16 .

21. A pharmaceutical dosage form made by the process of claim 17 .

22. A pharmaceutical dosage form made by the process of claim 18 .

Assignees

• Helsinn Healthcare Sa
• Ono Pharmaceutical Co

Inventors

• Kuwabe Shin-Itsu
• Yanagimachi Takehiko
• Yoshiyama Hideyuki
• Pines Seemon
• De Groot Eleanor
• Garcia Rubio Silvina
• Manini Peter

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K38/05 Primary

  Dipeptides · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title