Unlock instant, AI-driven research and patent intelligence for your innovation.

Parenteral formulation for epothilone analogs

Inactive Publication Date: 2006-01-19
R PHARMA US OPERATING LLC
View PDF24 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While these compounds possess significant therapeutic properties, they also present difficulties to those skilled in the art of pharmaceutical compounding, as a result of certain properties, as will be detailed hereinbelow.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Parenteral formulation for epothilone analogs
  • Parenteral formulation for epothilone analogs
  • Parenteral formulation for epothilone analogs

Examples

Experimental program
Comparison scheme
Effect test

example

[0061] [1S-[1R*,3R*(E),7R*,10S*, 11R*,12R*,16S*]]-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione, 9.86 g, was wetted / partially dissolved with 600 mL of a 9:1 mixture of tertiary butanol and Water for Injection USP which had been pre-cooled to 5° C. Once the drug powder had become completely wetted, dissolution was completed by the addition of 600 mL of a 1:9 mixture of tertiary butanol and Water for Injection and 766 mL of a 1:1 mixture of tertiary butanol and Water for Injection which likewise had been pre-cooled to 5° C. thereby making the final solution a 1:1 mixture. The dissolution was carried out under protection from light.

[0062] The solution formed above was promptly lyophilized in a Virtis INOTOP lyophilizer at −16° C. under light protectant conditions over a period of 48 hours. The resultant lyophilized product (lyophile) was then further dried at 15° C. under high vacuum for 48 hours. ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50% by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg / mL to about 0.9 mg / mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This is a continuation of application Ser. No. 10 / 051,727 filed on Jan. 17, 2002, now U.S. Pat. No. ______, which claims priority from provisional application Ser. No. 60 / 264,228, filed Jan. 25, 2001, both of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION [0002] The present invention relates to an improved formulation for parenteral administration of certain epothilone analogs that are characterized by enhanced clinical efficacy. BACKGROUND OF THE INVENTION [0003] Epothilones are macrolide compounds having utility in the pharmaceutical field. For example, Epothilones A and B having the structures: may be found to exert microtubule-stabilizing effects similar to paclitaxel (TAXOL®) and hence cytotoxic activity against rapidly proliferating cells, such as, tumor cells or other hyperproliferative cellular disease, see Hofle et al., Angew. Chem. Int. Ed. Engl., Vol. 35, No. 13 / 14, 1567-1569 (1996); WO 9...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/427A61K9/00C07D491/044A61K9/08A61K9/19A61K31/00A61K31/425A61K45/00A61K47/02A61K47/04A61K47/10A61K47/12A61K47/26A61K47/34A61P1/00A61P1/08A61P25/00A61P35/00A61P43/00
CPCA61K9/0019A61K9/0095A61K9/19A61K31/425A61K31/427A61K47/44A61K47/10A61K2300/00A61K31/395C07D491/044A61P1/00A61P1/08A61P25/00A61P35/00A61P43/00A61K9/00
Inventor BANDYOPADHYAY, REBANTAMALLOY, TIMOTHY M.PANAGGIO, ANDREARAGHAVAN, KRISHNASWAMY SRINIVASVARIA, SAILESH AMILAL
Owner R PHARMA US OPERATING LLC