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 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.
2. The pharmaceutical composition of claim 1 , wherein the oritavancin drug substance preparation has about 95% purity or greater by peak area.
3. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of mannitol, sorbitol, sucrose and trehalose.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is mannitol.
5. The pharmaceutical composition of claim 1 , wherein the ratio of the drug substance preparation to the one or more excipients is 2:1 by weight.
6. The pharmaceutical composition of claim 1 , wherein the purity level of the oritavancin drug substance preparation is measured by HPLC.
7. The pharmaceutical composition of claim 6 , 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).
8. 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 and impurity 10, defined by peaks B and J shown in FIG. 2 , respectively.
9. The pharmaceutical composition of claim 8 , wherein the oritavancin drug substance preparation has a maximum impurity level of not more than 3.0% by peak area.
10. The pharmaceutical composition of claim 8 , wherein the oritavancin drug substance preparation has a maximum impurity level of not more than 1.9% by peak area of impurity 2 and 2.9% by peak area of impurity 10.
11. The pharmaceutical composition of claim 8 , wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of mannitol, sorbitol, sucrose and trehalose.
12. The pharmaceutical composition of claim 8 , wherein the pharmaceutically acceptable excipient is mannitol.
13. The pharmaceutical composition of claim 8 , wherein the ratio of the drug substance preparation to the one or more excipients is 2:1 by weight.
14. The pharmaceutical composition of claim 8 , wherein the purity level of the oritavancin drug substance preparation is measured by HPLC.
15. The pharmaceutical composition of claim 14 , 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).