Methods of producing anamorelin hydrochloride having controlled chloride content

Patent metadata

Field	Value
Publication number	US-9403867-B2
Application number	US-201414539318-A
Country	US
Kind code	B2
Filing date	Nov 12, 2014
Priority date	Apr 20, 2012
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

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 ranging from 5.8 to 6.2%, a residual solvent concentration less than 1000 ppm, and an inter-batch chloride content that varies by no more than 7%.

2. The anamorelin monohydrochloride of claim 1 comprising less than 0.5% impurities.

3. The anamorelin monohydrochloride of claim 2 , wherein the impurities are selected from by-products, contaminants, and degradation products.

4. The anamorelin monohydrochloride of claim 3 , wherein said residual solvent is selected from the group consisting of methanol, butyl acetate, propyl acetate, ethyl acetate, isopropyl acetate, isobutyl acetate, methyl acetate, methylethyl ketone, methylisobutyl ketone, 2-methyltetrahydrofuran and combinations thereof.

5. The anamorelin monohydrochloride of claim 1 wherein the residual solvent is isopropyl acetate.

6. The anamorelin monohydrochloride of claim 1 having an inter-batch chloride content that varies by no more than 5%.

7. The anamorelin monohydrochloride of claim 1 having an inter-batch chloride content that varies by no more than 3%.

8. The anamorelin monohydrochloride of claim 1 in the substantial absence of anamorelin hydrochloride other than anamorelin monohydrochloride.

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

10. The anamorelin monohydrochloride of claim 1 in combination with one or more pharmaceutically acceptable excipients.

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

15. The anamorelin monohydrochloride of claim 1 having a stability defined by a percentage increase in impurities of no more than 340% when stored at 25° C. and a relative humidity of 60% for two years.

16. The anamorelin monohydrochloride of claim 1 having 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 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.

18. A pharmaceutical composition comprising:
a) a therapeutically effective amount of the anamorelin monohydrochloride of claim 1 ; and
b) one or more pharmaceutically acceptable excipients.

19. A method of making a pharmaceutical dosage form comprising:
a) combining a therapeutically effective amount of the anamorelin monohydrochloride of claim 1 with one or more pharmaceutically acceptable excipients to form a mixture; and
b) processing said mixture into a finished dosage form.

Assignees

• Helsinn Healthcare Sa
• Ono Pharmaceutical Co
• 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

• C07D401/12

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

• C07K5/06034 Primary

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

• C07D401/06 Primary

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

• A61K38/05 Primary

  Dipeptides · CPC title