Process for the Manufacture of Eptifibatide
Process for manufacturing eptifibatide which comprises subjecting a solution of eptifibatide derivative in a solvent to a concentration step, wherein the pH of said solution is less than or equal to 7.
1 . A process for manufacturing eptifibatide which comprises subjecting a solution of eptifibatide derivative in a solvent to a concentration step, wherein the pH of said solution is less than or equal to 7.
2 . The process according to claim 1 , wherein the pH of the solution is less than or equal to 5.
3 . The process according to claim 1 or 2 , wherein the pH of the solution is more than or equal to 3.
4 . The process according to anyone of claims 1 to 3 , wherein concentration step is carried out at a temperature less than or equal to 40° C.
5 . The process according to claim 4 , wherein the temperature is from 0 to 35° C.
6 . The process according to claim 5 , wherein the temperature is from 20 to 35° C.
7 . The process according to anyone of claims 1 to 6 , wherein the concentration step comprises evaporating solvent from the solution.
8 . The process according to claim 7 , wherein the solvent is evaporated at a pressure from 0.001 to 0.5 bars.
9 . The process according to anyone of claims 1 to 8 , wherein the solvent comprises water and a polar organic co-solvent.
10 . The process according to claim 9 which comprises evaporating a mixture of water and polar organic co-solvent.
11 . The process according to anyone of claims 1 to 10 , wherein the solvent comprises acetic acid.
12 . The process according to anyone of claims 1 to 11 , wherein the eptifibatide derivative contained in the solution consists essentially of eptifibatide (acetate).
13 . The process according to anyone of claims 1 to 12 , wherein the eptifibatide derivative concentration in the solution subjected to the concentration operation is from 0.5 to 3 wt. %.
14 . The process according to anyone of claims 1 to 13 , wherein the material recovered from the concentration operation is a concentrated solution of eptifibatide derivative.
15 . The process according to claim 14 , wherein the concentrated solution has an eptifibatide derivative concentration of from 4 to 5 wt. %.
16 . The process according to anyone of claims 1 to 15 , which comprises steps (a) to (d) wherein
(a) crude eptifibatide derivative is manufactured by coupling of peptide fragments;
(b) the crude eptifibatide derivative is subjected to a purification operation comprising at least one liquid chromatography operation to obtain a solution of eptifibatide derivative;
(c) the solution of eptifibatide derivative is subjected to the concentration step according to anyone of claims 1 to 15 to obtain material having increased concentration of eptifibatide; and
(d) the material having increased concentration of eptifibatide is subjected to a lyophilization operation to obtain eptifibatide.
17 . A solution of an eptifibatide derivative which contains from 0.5% wt. to 3% wt. of eptifibatide derivative in a solvent comprising water, a polar organic co-solvent and acetic acid.
18 . The solution according to claim 17 , which contains from 0.1 to 1 volume part of acetic acid per 100 volume parts of mixture of water/polar organic co-solvent.
19 . The solution according to claim 17 or 18 , wherein the polar organic co-solvent is acetonitrile.
20 . The solution according to anyone of claims 17 to 19 , wherein the eptifibatide derivative is eptifibatide (acetate).