Methods of producing anamorelin hydrochloride having controlled chloride content

Patent metadata

Field	Value
Publication number	US-9981002-B2
Application number	US-201615135051-A
Country	US
Kind code	B2
Filing date	Apr 21, 2016
Priority date	Apr 20, 2012
Publication date	May 29, 2018
Grant date	May 29, 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. Anamorelin monohydrochloride having a chloride content of from 5.6 to 6.3% by weight and a total residual solvent concentration less than 5000 ppm, wherein the residual solvent concentration excludes water.

2. The anamorelin monohydrochloride of claim 1 , wherein the residual solvent is selected from methanol, butyl acetate, propyl acetate, ethyl acetate, isopropyl acetate, isobutyl acetate, methyl acetate, methylethyl ketone, methylisobutyl ketone, isopropanol, 2-methyltetrahydrofuran and combinations thereof.

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

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

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

6. The anamorelin monohydrochloride of claim 1 , comprising less than 5% water.

7. The anamorelin monohydrochloride of claim 1 , comprising less than 3% water.

8. The anamorelin monohydrochloride of claim 1 , comprising less than 2% water.

9. The anamorelin monohydrochloride of claim 1 , in an isolated state.

10. A composition comprising anamorelin monohydrochloride in combination with one or more pharmaceutically acceptable excipients, wherein the anamorelin monohydrochloride has a chloride content ranging from 5.6 to 6.3% by weight, and a residual solvent concentration less than 5000 ppm for each solvent, wherein water is not a residual solvent.

11. The anamorelin monohydrochloride of claim 1 , in combination with one or more pharmaceutically acceptable excipients in the form a tablet or capsule or pellets or granules or powders.

12. The anamorelin monohydrochloride of claim 1 , having a solubility in water greater than 100 mg/mL.

13. The anamorelin monohydrochloride of claim 1 , having a solubility in water greater than 333 mg/mL.

14. Anamorelin monohydrochloride having a chloride content of from 5.6 to 6.2% by weight and a total residual solvent concentration less than 5000 ppm, wherein the residual solvent concentration excludes water.

15. The anamorelin monohydrochloride of claim 14 , 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.

16. The anamorelin monohydrochloride of claim 14 , 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.

17. The anamorelin monohydrochloride of claim 1 having a chloride content of from 5.6 to less than 6.3% by weight.

18. Anamorelin monohydrochloride having a chloride content of from 5.6 to 6.3% by weight and a total residual solvent concentration less than 5000 ppm, wherein the residual solvent concentration excludes water, and further wherein:
a. the anamorelin monohydrochloride has a solubility in water greater than 333 mg/mL;
b. 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;
c. the anamorelin monohydrochloride comprises less than 2% total impurities selected from by-products, contaminants, and degradation products; and
d. the anamorelin monohydrochloride comprises less than 3% water.

19. The anamorelin monohydrochloride of claim 18 , in combination with one or more pharmaceutically acceptable excipients in the form a tablet or capsule or pellets or granules or powders.

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

• C07K5/06034

  the side chain containing 2 to 4 carbon atoms · CPC title

• Y02P20/55

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

• C07D401/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D401/12

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