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. 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.