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Process for the preparation of Novel cabazitaxel Anisole Solvate

IP.com Disclosure Number: IPCOM000246330D
Publication Date: 2016-May-31

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The IP.com Prior Art Database

Related People

Dr. Madhuresh Kumar Sethi: AUTHOR

Related Documents

cabazitaxel: IP.COM

Abstract

Cabazitaxel is a semi synthetic taxoid derivative, used in combination with prednisone for the treatment of patients with castration-resistant metastasis, whose disease progresses after docetaxel treatment. Many solvates of Cabazitaxel have been published in patents. Different solvates may result in different physical properties. Thus, discovery of novel solvates yields an opportunity for further improvement of advantageous properties. The present disclosure relates to the preparation of cabazitaxel anisole solvate

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Process for the preparation of Novel cabazitaxel Anisole Solvate.

Madhuresh K Sethi*, Sanjay Mahajan, Bhairaiah Mara, Upendranath Veera, Anitha Nimmagadda, Srinivasarao Yelugoti and Purbita Chakraborty.

1 R & D, Mylan Laboratories Ltd., Plot No. 31, 32, 33 and 34 A ANRICH Industrial Estate, Bollaram (Village), Jinnaram (Mandal), Medak (Dt) 502325, Andhra Pradesh, India

* Corresponding author. E-mail: madhuresh.sethi@mylan.in

Abstract

Cabazitaxel is a semi synthetic taxoid derivative, used in combination with prednisone for the treatment of patients with castration-resistant metastasis, whose disease progresses after docetaxel treatment. Many solvates of Cabazitaxel have been published in patents. Different solvates may result in different physical properties. Thus, discovery of novel solvates yields an opportunity for further improvement of advantageous properties. The present disclosure relates to the preparation of cabazitaxel anisole solvate.

1.      Introduction

Cabazitaxel is the generic name for the trade name drug Jevtana®. In some cases, health care professionals may use the trade name Jevtana® when referring to the generic drug name cabazitaxel.

  • Jevtana is given through a vein (intravenously, IV)
  • There is no pill form of Jevtana.

Cabazitaxel chemically known as (2α, 5β, 7β, 10β, 13α)-4-acetoxy-13-({(2R, 3S)-3[(tertbutoxycarbonyl) amino]-2-hydroxy-3-phenylprop anoyl} oxy)-1-hydroxy-7, 10-dimethoxy-9-oxo-5, 20-epoxytax-11-en-2-yl benzoate has the structure as shown in figure –I

Anisole is listed as a Class III solvent with a default PDE of 50 mg/day (or more).  However, based upon the US labeling for Jevtana, the maximum dose (given once every three weeks) is 45 mg/day (25 mg/m2 * 1.80 m2) - thus, assuming that the 50 mg/day PDE value is sufficient for the formulation since the anisole content of the formulation would have to be greater than that of the API to exceed this PDE.

                                                    

Figure 1

Active pharmaceutical ingredients (APIs) are frequently administered in the solid state as approved dosage types (e.g. tablets, capsules and injectable etc.,), solids provide a generally stable vehicle for an API and drug product.APIs can exist in a variety of distinct solid forms, where each forms display unique physiochemical properties such as hygroscopicity, morphology, solubility and bioavailability.(1)   

2.      Experimental procedure:

2.1 Process for the preparation of cabazitaxel anisole solvate

A mixture of 4a-acetoxy-2a-benzoyloxy-5P, 20-epoxy-i p- hydroxy, 7β, 1 Οβ-dimethoxy- 9-oxo-l l-taxene-13a-yl (2R, 4S, 5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4- phenyl-1, 3-oxazolidine-5-carboxylate (3.7 g) and ~ 0.2 N hydrochloric acid in ethanol (89 ml), was stirred under nitrogen atmosphere at a temperature of 0-5 °C. Dichloromethane (150 ml) and sodium bicarbonate solution (7.0 g sodium bicarbonate dissolved in 56 ml of water) were add...