Palonosetron free base and process for its preparation
The present invention provides novel palonosetron free base in an amorphous form and crystalline form-G and processes for their preparation. The present invention also provides a process for the preparation of palonosetron hydrochloride from the novel palonosetron free base in an amorphous form and/or in crystalline form-G.
1. Isolated palonosetron free base in solid crystalline form-G, having an X-ray diffraction pattern in accordance with FIG. 4 , and a differential scanning calorimetric thermogram, with a predominant endotherm peak at about 95.71° C., in accordance with FIG. 5 .
2. A process for the preparation of palonosetron free base in solid crystalline form-G of claim 1 comprising
a) hydrogenating the 2-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one of formula-II with a hydrogenation catalyst, in water;
b) isolating the palonosetron free base in solid form using a suitable organic solvent.
3. The process of claim 2 , further comprising converting the palonosetron free base in solid form into a pharmaceutically acceptable salt thereof.
4. A process for the preparation of palonosetron free base in crystalline form-G of claim 1 , comprising;
a) providing a solution of palonosetron hydrochloride in a water immiscible organic solvent and water;
b) treating the solution with a base;
c) concentrating the water immiscible organic solvent; and
d) crystallizing the resultant residue in a suitable organic solvent.
5. The process of claim 4 , wherein the water immiscible organic solvent is dichloromethane, toluene, or ethyl acetate.
6. The process of claim 5 , wherein the crystallizing solvent is methanol, ethyl acetate, water and mixtures thereof.
7. A process for the preparation of palonosetron hydrochloride, comprising:
a) providing a solution of palonosetron free base in solid form obtained from the process of claim 2 ;
b) treating the solution in a) with an aqueous or an anhydrous hydrochloric acid,
c) isolating the palonosetron hydrochloride.
8. The palonosetron free base in solid crystalline form-G of claim 1 , in form of a hydrochloride salt and, having less than about 0.11% of 2-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one of formula-II, as determined by high performance liquid chromatography