WO2012156999A4

WO2012156999A4 - Ready to use docetaxel formulation

Info

Publication number: WO2012156999A4
Application number: PCT/IN2012/000358
Authority: WO
Inventors: Manu Chaudhary
Original assignee: Individual
Current assignee: Individual
Priority date: 2011-05-19
Filing date: 2012-05-21
Publication date: 2013-01-10
Anticipated expiration: 2013-11-19
Also published as: WO2012156999A1

Abstract

A single vial stabilized liquid formulation of taxane derivative, adapted to be used directly to a perfusion/infusion solution for administration into a subject in need is provided. The formulation includes an effective amount of : docetaxel or a pharmaceutically acceptable salt thereof; one ore more surfactant; one or more co-surfactant; water for injection; and one or more organic acid. The particle size of the formulation is in a range of 20 nm to 100nm and the pH of the formulation is in a range of about 3.5 to 4.

Claims

AMENDED CLAIMS received by the International Bureau on 16 November 2012 (16.1 1.2012) We Claim:

1. A single vial stabilized liquid formulation of taxane derivative, adapted to be used direcdy to a perfusion/infusion solution for administration into a subject in need, said formulation comprising an effective amount of :

docetaxel or a pharmaceutically acceptable salt thereof;

at least one surfactant;

at least one co-surfactant;

water for injection; and

at least one organic acid,

wherein particle size of docetaxel is in a range of 20 nm to lOOnm; and

wherein pH of the formulation is in a range of about 3.5 to 4.

2. The single vial stabilized liquid formulation of claim 1,

wherein said formulation is stable for a peridd of more than 6 months at a temperature of about 40°C .

3. The single vial stabilized liquid formulation of claim 1,

wherein said formulation is stable for a period of minimum 6 months to 24 months at a temperature range of 15° C to 25 ⁰ C.

4. The single vial stabilized liquid formulation of claim 1,

wherein said formulation is stable for a period of more than 2 years at a temperature range of 2° C to 8° C.

5. The single vial stabilized liquid formulation of claim 1, wherein amount of docetaxel is 40mg/ ml.

6. The single vial stabilized liquid formulation of claim 1,

wherein said surfactant is polysorbate 80.

7. The single vial stabilized liquid formulation of claim 1,

wherein said surfactant is present in an amount of 50 ± 5% v/v , preferably 52.46% v/v.

8. The single vial stabilized liquid formulation of claim 1,

wherein said co-surfactant is ethanol.

9. The single vial stabilized liquid formulation of claim 1, wherein said co-surfactant is is present in an amount preferably40.9% v/v.

10. The single vial stabilized liquid formulation of claim 1,

wherein said organic acid is selected from the group consisting of citric acid, tartaric acid, acetic acid or a combination thereof.

11. The single vial stabilized liquid formulation of claim 1, wherein said organic acid is present in an amount preferably 9.5mM to adjust pH between 3.5 to 4.

12. The single vial stabilized liquid formulation of claim 1, wherein said organic acid is citric acid.

13. The single vial stabilized liquid formulation of claim 1, wherein water for injection is present in an amount preferably 5±2%.

14. The single vial stabilized formulation of claim 1, wherein said formulation is present in the form of micronised nanao particles, self- nanoemuslsifying formulation, miceller nano particle.

15. A process of preparation of the single vial stabilized liquid formulation of claim 1, said process comprising the step of :

constant stirring of 50 ± 5% v/v of surfactant and 9.5mM citric acid solution at < 500 rpm for 20-30 minutes under inert gas atmosphere to obtain an initial solution,

wherein temperature is maintained at 20±5° C ; and

wherein citric acid solution is added to adjust the pH to about 3.5 to 4 ; addition of 40±5% v/v of co-surfactant with lowering of temperature to 2-8° C at < 500 rpm for 20-30 minutes under inert gas to obtain an intermediate solution; and

addition of 20mg to 120 mg docetaxel into the intermediate solution under constant stirring until complete dissolution of docetaxel to obtain a clear solution of formulation.

16. The process of preparation of claim 1,

wherein said surfactant is polysorbate 80;

wherein said co-surfactant is ethyl alcohol.

17. Use of single vial stabilized formulation of claim 1 for preparation of a medicament for

treatment of disease condition selected from the group comprising of non-small cell lung, breast, ovarian, head cancer, cervical cancer and brain cancer.

18. A method of treating disease condition selected from the group comprising of non-small cell lung, breast, ovarian, head cancer, cervical cancer and brain cancer comprising administering to a patient in need of such treatment an effective amount of single vial stabilized formulation of claim 1, wherein said formulation is administered directly to an infusion/perfusion solution.