Process and formulation containing epothilones and analogs thereof

• US 8,871,227 B2
• Filed: 09/11/2009
• Issued: 10/28/2014
• Est. Priority Date: 11/04/2003
• Status: Active Grant

• Current Assignee: R-pharm us operating llc
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Haby, Thomas A., Gogate, Uday S., Naringrekar, Vijay H.
• Primary Examiner(s): Maewall, Snigdha
• Application Number:
  US12/557,822
• Publication Number:
  US 20100016385A1
• Time in Patent Office: 1,873 Days
• Field of Search: None
• US Class Current: 424/400
• CPC Class Codes: A61K 31/425 Thiazoles

Abstract

A process for formulating certain epothilones and analogs thereof for parenteral administration is provided wherein the pH of the formulation for administration can be controlled to enhance the stability and thus, potency of the epothilone, or analog thereof.

Claims

1. A pharmaceutical formulation for parenteral administration as a solution of an epothilone analog to a patient, the epothilone analog having the formula:

2. The pharmaceutical formulation of claim 1 wherein the pH-adjusting ingredient is a base, and the pharmaceutical formulation consists essentially of the epothilone analog compound, buffer, the base, the alcohol, and a nonionic surfactant.

3. The pharmaceutical formulation of claim 1 wherein the infusion fluid is saline, and the pharmaceutical formulation has a pH in the range from 6 to 9.

4. The pharmaceutical formulation of claim 1 wherein the infusion fluid of the formulation for administration is dextrose, the pharmaceutical formulation has a pH in the range from 6 to 9.

7. A kit for preparing a formulation for parenteral administration as defined in claim 1, the formulation for parenteral administration comprising:

i) an infusion fluid having an infusion fluid pH which infusion fluid is selected from the group consisting essentially of saline and dextrose and free of Lactated Ringer'"'"'s Solution; and

ii) an epothilone analog compound of the formula;

8. The kit of claim 7, wherein the epothilone analog compound in the first vial is lyophilized, and the pharmaceutical preparation in the second vial is a reconstitution vehicle.

5. A process for parenterally administering to a patient an epothilone analog compound, with an infusion fluid which is dextrose or saline and excludes Lactated Ringer'"'"'s Solution having an infusion fluid pH, the compound having the formula,

6. The process of claim 5, wherein the solution vehicle is prepared to achieve a pH in the range of about 6 to about 9.