DESC:The following specification particularly describes the invention and the manner in which it is to be performed:

PROCESS FOR THE PREPARATION OF POLYMORPHIC FORMS OF NILOTINIB HYDROCHLORIDE

INTRODUCTION
The present application provides process for the preparation of polymorphic form R6 of Nilotinib hydrochloride.
BACKGROUND OF THE INVENTION
The drug compound having the adopted name “nilotinib hydrochloride” has a chemical name 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl) phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide monohydrochloride, and is structurally represented by Formula I.

Formula I
Nilotinib hydrochloride is a kinase inhibitor, approved as nilotinib hydrochloride monohydrate, sold using the trade name Tasigna®, in the form of capsule for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included imatinib.
International application publication No. WO2007/015871 A1 describes salts of 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl] amino]-benzamide, wherein the salt is a hydrochloride salt, hydrochloride monohydrate, monophosphate salt, diphosphate salt, sulfate salt, methanesulfate salt, ethanesulfonate salt, benzene sulfonate salt, p-toluene sulfonate salt, citrate salt, furmarate salt, malonate salt, malate salt, tartrate salt, etc., their polymorphic forms and process for the preparation thereof. Further, it also discloses the crystalline forms of nilotinib hydrochloride designated as Form A and Form B, process for their preparation and process for the preparation of nilotinib hydrochloride monohydrate.
International application publication No. WO2007/015870 A2 describes substantially pure crystalline forms of nilotinib hydrochloride designated as Form A, Form A’, Form A’’, Form B, Form B’, Form SB, Form SB’, Form C, Form C’, Form SC, Form D, Form SE, mixture of Form B and Form D, and amorphous form of Nilotinib hydrochloride. Further, it also discloses substantially pure crystalline forms A and B of Nilotinib free base and substantially pure crystalline forms A and B of Nilotinib sulfate salt.
International application publication No. WO2010/054056 A2 describes polymorphic forms of nilotinib hydrochloride designated as forms T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, T15 T16, T17, T18, and T19. Further, it also describes solid dispersion of nilotinib hydrochloride in combination with a pharmaceutically suitable excipient.
International application publication No. WO2011/163222 describes polymorphic forms of nilotinib hydrochloride designated as forms T20, T27, T28 and T29.
International application publication No. WO2011/086541 A1 describes a crystalline form of nilotinib hydrochloride monohydrate having an X-ray diffraction pattern comprising peaks at 5.70, 7.56, 9.82, 15.01, 17.31 and 27.68 ± 0.2 degrees 2-theta and process for its preparation.
International application publication No. WO2012/055351 A1 describes a crystalline form of nilotinib hydrochloride monohydrate having an X-ray diffraction pattern comprising peaks at 4.987, 8.430, 11.309, 14.403, 17.219, 19.225 and 25.544 degrees 2-theta and process for its preparation.
International application publication No. WO2012/070062 A2 describes nilotinib hydrochloride crystalline form H1, characterized by peaks in the powder x-ray diffraction spectrum having 2-theta angle positions at about 8.6, 11.4, 13.2, 14.3, 15.5, 17.3, 19.2 and 25.3 ± 0.2 degrees and process for its preparation.
US application publication No. 2013/0210847 A1 describes nilotinib hydrochloride dihydrate, characterized by peaks in the powder X-ray diffraction pattern at 4.3, 8.7, 9.5, 11.3, 13.2, 14.4, 17.3, 18.6, 19.3, 20.8, 22.2 and 25.3 degrees 2-theta (± 0.1 degrees 2-theta).
IP.com Journal (2010), 10(3B), 11 describes the crystalline forms T24, T25, and T26 of nilotinib hydrochloride and process for their preparation.
IP com Journal (2010), 10(12A), 18 describes the crystalline forms of nilotinib hydrochloride designated as Forms T19 and T20 and process for their preparation.
IP.com Journal (2009), 9(12B), 14 describes the nilotinib hydrochloride crystalline forms T2-T6, T9 and T11-T13 and process for their preparation.
IP.com Journal (2010), 10(5A), 25 describes the nilotinib hydrochloride crystalline form T5 and process for its preparation.
IP.com Journal (2010), 10(7B), 3 describes a method for the preparation of the 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzamide salts in amorphous form.
The discovery of new polymorphic forms and/or solvates of a drug or a pharmaceutically useful compound provide opportunity to improve the characteristics of a pharmaceutically acceptable dosage form of the drug with a targeted release profile or other desired characteristics.
The PCT application number PCT/IB2014/060935 discloses the forms R5 and R6 of nilotinib hydrochloride.
Despite the aforementioned disclosures mentioning various processes, there is a need for improved process for the preparation of polymorphic forms of nilotinib hydrochloride.
SUMMARY OF THE INVENTION
In an aspect, the present application provides a process for preparing a crystalline nilotinib hydrochloride Form R6, characterized by X-ray powder diffraction pattern having peaks at about 7.56 ? 0.2, 10.16 ? 0.2, 12.42 ? 0.2, 20.32 ? 0.2 and 27.97 ? 0.2 degrees 2-theta; an x-ray powder diffraction pattern with peaks at about 8.93 ? 0.2, 11.76 ? 0.2, 15.53 ? 0.2, 17.71 ? 0.2, 19.57 ? 0.2, 21.72 ? 0.2 and 23.40 ? 0.2 degrees 2-theta; an x-ray powder diffraction pattern substantially as depicted in Figure 2, by drying crystalline Form R5 using microwave heating.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 illustrates a characteristic X-ray powder diffraction pattern of nilotinib hydrochloride Form R5.
Figure 2 illustrates a characteristic X-ray powder diffraction pattern of nilotinib hydrochloride Form R6 obtained as per example 1.
Figure 3 illustrates a characteristic X-ray powder diffraction pattern of nilotinib hydrochloride Form R6 obtained as per example 2.
DETAILED DESCRIPTION
In an aspect, the present application provides a process for preparing a crystalline nilotinib hydrochloride Form R6, characterized by X-ray powder diffraction pattern having peaks at about 7.56 ? 0.2, 10.16 ? 0.2, 12.42 ? 0.2, 20.32 ? 0.2 and 27.97 ? 0.2 degrees 2-theta; an x-ray powder diffraction pattern with peaks at about 8.93 ? 0.2, 11.76 ? 0.2, 15.53 ? 0.2, 17.71 ? 0.2, 19.57 ? 0.2, 21.72 ? 0.2 and 23.40 ? 0.2 degrees 2-theta; an x-ray powder diffraction pattern substantially as depicted in figure 2, by drying crystalline Form R5 using microwave heating.

According to an aspect of the invention, the drying is carried out under microwave radiation, for example, in a microwave oven.
In an embodiment, a microwave oven having a power output range of (180-900 Watts) with five levels operated at a frequency of 2450 MHz is used. Any other suitable frequency may also be employed.
Microwave irradiation may be combined with convection mode for faster conversions. The convection mode can go upto temperature of 180°C. The irradiation time intervals can range from 10 seconds to 10minutes.
The exposure time of the material to microwave radiation may be varied for a period of about 30 minutes to about 90 minutes.

Examples
Example 1: Preparation of Nilotinib hydrochloride Form R6
3.0 g of nilotinib hydrochloride form R5 was taken in a petri dish and was exposed to heating in a microwave oven, which has a output of 900 watts and is operated at a frequency of 2450 MHz. The material was exposed to the microwave irradiation for a period of about 30 minutes by disturbing the material after every 2 minutes to obtain the title compound.
Example 2: Preparation of Nilotinib hydrochloride Form R6
5.0 g of nilotinib hydrochloride form R5 was taken in a petri dish and was exposed to heating in a microwave oven, which has a output of 900 watts and is operated at a frequency of 2450 MHz. The material was exposed to the microwave irradiation for a period of about 70 minutes by disturbing the material after every 2 minutes to obtain the title compound.
,CLAIMS:We Claim:

1. A process for the preparation of crystalline nilotinib hydrochloride Form R6 by drying crystalline nilotinib hydrochloride Form R5 using microwave heating.
2. The process of claim 1 wherein, the microwave heating is microwave radiation
3. The process of claim 2 wherein, the microwave radiation has a frequency of 2450 MHz.