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 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.