Methods of producing anamorelin hydrochloride having controlled chloride content
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.
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 .