1. A process for producing rosuvastatin calcium comprising:
a) reacting a C1 to C4 alkyl ester of rosuvastatin with a base in presence of a C1 to C4 alcohol to obtain a solution;
b) concentrating the solution to obtain a residue;
c) combining the residue with water to obtain an aqueous solution;
d) washing the aqueous solution with a water immiscible organic solvent;
e) removing traces of the organic solvent;
f) adding a source of calcium to the solution to precipitate rosuvastatin calcium; and
g) recovering the rosuvastatin calcium salt.
2. The process of claim 1, wherein the ester is a methyl ester.
3. The process of claim 1, wherein the ester is a t-butyl ester.
4. The process of claim 1, further comprising the step of stirring before step (b).
5. The process of claim 1, wherein concentrating in step (b) is carried out by evaporation.
6. The process of claim 5, wherein evaporation is carried out under reduced pressure.
7. The process of claim 1, wherein reacting is carried out by adding the base to a suspension of the ester in the alcohol.
8. The process of claim 7, wherein the alcohol is ethanol.
9. The process of claim 1, wherein the organic solvent is a C4 to C7 ester or ketone.
10. The process of claim 9, wherein the ester is ethylacetate.
11. The process of claim 1, wherein removing in step (e) is carried out by evaporation.
12. The process of claim 11, wherein the evaporation is carried out under reduced pressure.
13. The process of claim 1, wherein the source of calcium is calcium chloride.
14. The process of claim 1, wherein the recovering step is carried out with filtration.
15. The process of claim 1, wherein the base is selected from the group consisting of sodium, potassium and barium hydroxide.
16. A process for producing rosuvastatin calcium salt comprising:
a) combining a suspension of t-butyl ester of rosuvastatin in ethanol with sodium hydroxide to obtain a solution, and stirring during or after the combining;
b) evaporating the solution under reduced pressure to obtain a residue;
c) combining the residue with water to obtain an aqueous solution;
d) washing the aqueous solution with ethyl acetate;
e) evaporating traces of the ethyl acetate under reduced pressure;
f) adding calcium chloride to the solution to precipitate rosuvastatin calcium; and
g) filtering the rosuvastatin calcium salt.
17. A process for producing rosuvastatin calcium salt comprising:
a) reacting a C1 to C4 alkyl ester of rosuvastatin in a water immiscible phase, with a base in an aqueous phase, in presence of a phase transfer catalyst to obtain rosuvastatin in the aqueous phase;
b) adding a source of calcium to the aqueous phase to precipitate rosuvastatin calcium; and
c) recovering the rosuvastatin calcium salt; with the proviso that:
(i) the process further comprising a step of removing traces of the water immiscible solvent before adding a source of calcium; wherein the ester is a t-butyl ester:
(ii) the process further comprises stirring during the reaction;
(iii) wherein the water immiscible phase is a solvent selected from the group consisting of substituted and unsubstituted C5 to C12 hydrocarbon, C4 to C7 ester, C4 to C7 ketone and mixtures thereof; or
(iv) the hydrocarbon is toluene or chlorobenzene.
18. The process of claim 17, further comprising a step of removing traces of the water immiscible solvent before adding a source of calcium.
19. The process of claim 17, wherein the ester is a t-butyl ester.
20. The process of claim 17, further comprising stirring during the reaction.
21. The process of claim 17, wherein the water immiscible phase is a solvent selected from the group consisting of substituted and unsubstituted C5 to C12 hydrocarbon, C4 to C7 ester, C4 to C7 ketone and mixtures thereof.
22. The process of claim 21, wherein the hydrocarbon is toluene or chlorobenzene.
23. The process of claim 17, wherein the phase transfer catalyst is an alkyl, aryl, alkaryl or arylalkyl ammonium salt.
24. A process for producing rosuvastatin calcium salt comprising:
a) reacting, t-butyl ester of rosuvastatin with sodium hydroxide in presence of water, a tetrabutylammonium phase transfer catalyst and an organic solvent selected from the group consisting of toluene and chlorobenzene to obtain rosuvastatin in the water;
b) removing traces of the toluene or chlorobenzene from the water;
c) adding calcium chloride to the water to precipitate rosuvastatin calcium; and
d) filtering the rosuvastatin calcium salt.
25. The process of claim 24, further comprising stirring during the reaction.
26. A process for producing rosuvastatin calcium salt substantially free of impurities comprising the steps of:
a) reacting a C1 to C4 ester of rosuvastatin with a base in a two phase system of water and acetonitrile;
b) concentrating the water phase to obtain a residue;
c) adding a source of calcium and water to the residue to form a solution in water; and
d) recovering rosuvastatin calcium as a precipitate.
27. The process of claim 26, further comprising stirring during the reaction.
28. The process of claim 1, 16, 17, 24, or 26, wherein the calcium salt contains less than or of about 0.4% total impurities as measured by area percentage HPLC.
29. The process of claim 28, wherein the impurities is of or less than about 0.3% as measured by area percentage HPLC.
30. The process of claim 1, 16, 17, 24, or 26, wherein the calcium salt does not have detectable level of impurities when measured by HPLC at RRT 0.62, 1.18, 1.26, 1.60, 2.68, 3.66, 3.89, 3.93 and 4.10.
31. The process of claim 30, wherein the impurities are less than about 0.01% as measured by HPLC area percentage.
32. A process for producing rosuvastatin calcium comprising:
a) preparing a solution of rosuvastatin sodium;
b) concentrating the solution to obtain a residue;
c) combining the residue with water to obtain an aqueous solution;
d) washing the aqueous solution with a water immiscible organic solvent;
e) removing traces of the organic solvent;
f) adding a source of calcium to the solution to precipitate rosuvastatin calcium; and
g) recovering the rosuvastatin calcium salt.
33. Rosuvastatin calcium in solid state having less than or of about 0.4% total impurities as measured by area percentage HPLC.
34. The rosuvastatin calcium of claim 33, wherein the impurities is of or less than about 0.3% as measured by area percentage HPLC.
35. Rosuvastatin calcium in solid state, wherein the calcium salt does not have detectable level of impurities when measured by HPLC at RRT 1.26.
36. The rosuvastatin calcium of claim 35, wherein the calcium salt does not have further detectable level of impurities when measured by HPLC at RRT 0.62, 1.18, 1.60, 2.68, 3.66, 3.89, 3.93 and 4.10.
37. The rosuvastatin calcium of claim 36, wherein the impurities are less than about 0.01% as measured by HPLC area percentage.
38. The process of claim 1, 16, 17, 24, or 26, wherein the process is performed in one-pot.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A printer cartridge comprising:
a housing having a plurality of surfaces;
a first chamber within the housing;
a second chamber within the housing;
a first fluidic interconnect that receives fluid and directs the fluid to the first chamber having an axis that is perpendicular to a direction of fluid flow out of the printer cartridge formed within one of the plurality of surfaces; and a second fluidic interconnect formed within one of the plurality of surfaces and fluidically coupled with the second chamber.
2. The printer cartridge of claim 1 further comprising a filter separating the first and second chambers.
3. The printer cartridge of claim 2 further comprising a printhead formed along one of the outer surfaces of the housing adjacent the second chamber.
4. The printer cartridge of claim 1 further comprising an air purge mechanism along one of the outer surfaces adjacent the first chamber.
5. The printer cartridge of claim 4 further comprising a printhead with nozzles, wherein the air purge mechanism purges air from the nozzles.
6. The printer cartridge of claim 1 further comprising an indicator that shows a fluid level in the cartridge.
7. A printer cartridge comprising:
a housing enclosing fluid, the housing having a printhead ejecting the fluid;
a pressurized chamber within the housing;
an exit fluidic interconnect in the housing that is capable of extracting the fluid from the pressurized chamber; and
an entrance fluidic interconnect having an axis that is perpendicular to a direction of fluid flow out of the printer cartridge that is capable of inserting the fluid into the pressurized chamber.
8. The printer cartridge of claim 7 wherein the fluid includes at least one of liquid and gasses.
9. The printer cartridge of claim 7 wherein the pressurized chamber includes a capillary chamber coupled with the entrance fluidic interconnect and a filtered chamber coupled with the exit fluidic interconnect.
10. The printer cartridge of claim 7 wherein the pressurized chamber has an internal pressure regulator.
11. A fluid ejection cartridge comprising:
a housing having a plurality of surfaces;
a first chamber within the housing;
a second chamber within the housing;
a first fluidic interconnect that receives fluid and directs the fluid to the first chamber having an axis that is perpendicular to a direction of fluid flow out of the fluid ejection cartridge formed within one of the plurality of surfaces; and
a second fluidic interconnect formed within one of the plurality of surfaces and fluidically coupled with the second chamber.
12. The fluid ejection cartridge of claim 11 further comprising an air purge mechanism along one of the outer surfaces adjacent the first chamber.
13. A fluid ejection cartridge comprising:
a housing enclosing fluid, the housing having a printhead ejecting the fluid;
a pressurized chamber within the housing;
an exit fluidic interconnect in the housing that is capable of extracting the fluid from the pressurized chamber; and
an entrance fluidic interconnect having an axis that is perpendicular to a direction of fluid flow out of the fluid ejection cartridge in the housing that is capable of inserting the fluid into the pressurized chamber.