High purity oritavancin and method of producing same
View Patent ↗Drug substance preparations of oritavancin having high purity are disclosed, along with pharmaceutical compositions comprising such oritavancin drug substance preparations, and drug products or dosage forms comprising such pharmaceutical compositions.
1. A method for preparing a pharmaceutical composition comprising an oritavancin drug substance preparation and one or more pharmaceutically acceptable excipients, wherein the oritavancin drug substance preparation has about 90% purity or greater by peak area relative to impurities 2-16, defined by peaks B-P of FIG. 2 , respectively, said method comprising:
a) dissolving one or more pharmaceutically acceptable excipients in water having a pH of 2.5 to 3.5 to form a solution,
b) dissolving oritavancin drug substance preparation in the solution of a) and adjusting the pH of the solution to 3.5 to 4.0,
c) filtering the solution of b), and
d) lyophilizing the filtered solution of c).
2. The method of claim 1 , wherein the oritavancin drug substance preparation has about 95% purity or greater by peak area.
3. The method of claim 1 , wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of mannitol, sorbitol, sucrose and trehalose.
4. A method of preparing a pharmaceutical composition comprising an oritavancin drug substance preparation and one or more pharmaceutically acceptable excipients, wherein the oritavancin drug substance preparation has a maximum impurity level of not more than 4.8% by peak area of impurity 2 (DEV A) and impurity 10 (oritavancin CR), defined by peaks B and J shown in FIG. 2 , respectively, said method comprising:
a) dissolving one or more pharmaceutically acceptable excipients in water having a pH of 2.5 to 3.5 to form a solution,
b) dissolving oritavancin drug substance preparation in the solution of a) and adjusting the pH of the solution to 3.5 to 4.0,
c) filtering the solution of b), and
d) lyophilizing the filtered solution of c).
5. The method of claim 4 , wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of mannitol, sorbitol, sucrose and trehalose.
6. The method of claim 1 , wherein the lyophilizing achieves a level of moisture of less than about 5% by weight.
7. The method of claim 1 , wherein the pharmaceutically acceptable excipient is mannitol.
8. The method of claim 1 , wherein the ratio of the drug substance preparation to the one or more excipients is 2:1 by weight.
9. The method of claim 1 , wherein the purity level of the oritavancin drug substance preparation is measured by HPLC.
10. The method of claim 9 , wherein the purity level of the oritavancin drug substance preparation is measured by HPLC, and wherein the HPLC measurement utilizes a C18 reverse-phase stationary phase and a gradient of mobile phase B, which is phosphoric acid/water/acetonitrile/tetrahydrofuran at a ratio of about 1/1000/1500/25 (v/v/v/v), in mobile phase A, which is phosphoric acid/water/tetrahydrofuran at a ratio of about 1/1000/10 (v/v/v).