Solid Forms Of Asciminib Hydrochloride

DESC:SOLID FORMS OF ASCIMINIB HYDROCHLORIDE INTRODUCTION The present invention provides crystalline forms of Asciminib hydrochloride and its process for the preparation and pharmaceutical composition thereof. The drug compound having the adopted name “Asciminib hydrochloride” has chemical name: N-[4(Chloro(difluoro)methoxy) phenyl]-6- [(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-3-yl)pyridine-3-carboxamide hydrogen chloride of formula (I) as below. Formula (I) Asciminib HCl is a allosteric BCR-ABL inhibitor developed and marketed by Novartis as SCEMBLIX oral tablet for the treatment for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). The US 8829195 B2 patent first disclosed Asciminib or the pharmaceutically acceptable salt generically and specifically and its use thereof for the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). Subsequently, the WO2020230099A1 patent application described crystalline forms of Asciminib hydrochloride (Form A, Form B and Form HA). Also described the crystalline forms of Asciminib free base (Form A, Form SA, Form SB, Form SC and Form SD). The WO2021154980A1 patent application discloses crystalline forms DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 3 of Asciminib hydrochloride and its process. Also discloses crystalline forms of Asciminib mesylate and Asciminib bromide and their process. However, there remains a need for alternate solid forms of Asciminib hydrochloride and preparative processes thereof, exhibiting desired properties such as bioavailability and stability. Hence, it is desirable to provide a viable solid form of Asciminib hydrochloride. Different forms of Active pharmaceutical ingredients (API) in pharmaceutical compositions can be prepared. In the synthesis of a chemical compound intended for pharmaceutical use, it is necessary to isolate and purify the compound at the completion of the synthetic process and prior to further processing to provide the compound in a pharmaceutical formulation. The isolation and the purification steps, which can be combined or separate consecutive steps, provide the compound as a purified solid with minimal loss of yield during isolation from other components of the reaction mixture and/or during purification to remove impurities from the isolated compound sample. It is desirable to prepare physically and chemically stable crystalline form using regulatory acceptable solvents. SUMMARY In the first aspect, the present invention provides a crystalline form AH1 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 4.8, 15.2 ± 0.2° 2?. In an embodiment, the application provides a crystalline form AH1 of Asciminib hydrochloride, characterized by a PXRD having additional peaks at about 9.7, 16.9 and 27.3 ± 0.2° 2?. In the second aspect, the present invention provides a process for preparation of crystalline form AH1 of Asciminib hydrochloride, comprising; a) grinding or contacting Asciminib free base in Sulfolane solvent; b) adding aqueous hydrochloride to the mixture of step a); c) isolating crystalline form AH1 of Asciminib hydrochloride. In the third aspect, the present invention provides a crystalline form AH2 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 4.9, 21.4 ± 0.2° 2?. In an embodiment, the application provides a crystalline DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 4 form AH2 of Asciminib hydrochloride, characterized by a PXRD having additional peak at about 10.8, 13.4, 15.2, 18.3 ± 0.2° 2?. In the fourth aspect, the present invention provides a process for preparation of crystalline form AH2 of Asciminib hydrochloride, comprising; a) providing a mixture of Asciminib hydrochloride in alcohol solvent; b) isolating crystalline form AH2 of Asciminib hydrochloride. In the fifth aspect, the present invention provides a crystalline form AH3 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 8.2, 18.3 ± 0.2° 2?. In an embodiment, the application provides a crystalline form AH3 of Asciminib hydrochloride, characterized by a PXRD having additional peak at about 6.8, 10.8 and 13.3 ± 0.2° 2?. In the sixth aspect, the present invention provides a process for preparation of crystalline form AH3 of Asciminib hydrochloride, comprising; a) providing a mixture of Asciminib in alcoholic hydrochloride; b) isolating crystalline form AH3 of Asciminib hydrochloride. In the seventh aspect, the present application provides a pharmaceutical composition comprising crystalline Form of Asciminib hydrochloride selected from the group comprising Form AH1, Form AH2 and Form AH3 or mixtures thereof together with at least one pharmaceutically acceptable excipient. BRIEF DESCRIPTION OF THE DRAWING Figure 1 is an illustrative X-ray powder diffraction of crystalline Form AH1 of Asciminib hydrochloride prepared by the method of Example-1. Figure 2 is an illustrative X-ray powder diffraction of crystalline Form AH2 of Asciminib hydrochloride prepared by the method of Example-2. Figure 3 is an illustrative X-ray powder diffraction of crystalline Form AH3 of Asciminib hydrochloride prepared by the method of Example-3. DETAILED DESCRIPTION In the first aspect, the present invention provides a crystalline form AH1 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 5 4.8, 15.2 ± 0.2° 2?. In an embodiment, the application provides a crystalline form AH1 of Asciminib hydrochloride, characterized by a PXRD having additional peaks at about 9.7, 16.9 and 27.3 ± 0.2° 2?. In an embodiment, the present application provides crystalline form AH1 of Asciminib hydrochloride, characterized by a PXRD substantially as shown in Figure 1. In the second aspect, the present invention provides a process for preparation of crystalline form AH1 of Asciminib hydrochloride, comprising; a) grinding or contacting Asciminib free base in Sulfolane solvent; b) adding aqueous hydrochloride to the mixture of step a); c) isolating crystalline form AH1 of Asciminib hydrochloride. The grinding process comprises grinding of Asciminib with aqueous hydrochloric acid in sulfolane solvent. In grinding process, Asciminib and aqueous hydrochloric acid in sulfolane solvent grind in a mortar, a grinder or a mill to obtain a crystalline form AH1 of Asciminib hydrochloride. Grinding in a mortar involves physical grinding of Asciminib and aqueous hydrochloric acid in sulfolane solvent. In the third aspect, the present invention provides a crystalline form AH2 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 4.9, 21.4 ± 0.2° 2?. In an embodiment, the application provides a crystalline form AH2 of Asciminib hydrochloride, characterized by a PXRD having additional peak at about 10.8, 13.4, 15.2, 18.3 ± 0.2° 2?. In an embodiment, the present application provides crystalline form AH2 of Asciminib hydrochloride, characterized by a PXRD substantially as shown in Figure 2. In the fourth aspect, the present invention provides a process for preparation of crystalline form AH2 of Asciminib hydrochloride, comprising; a) providing a mixture of Asciminib hydrochloride in alcohol solvent; b) isolating crystalline form AH2 of Asciminib hydrochloride. In embodiments of step a) involves the solution may optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 6 material to remove color and/or to clarify the solution. Suitable alcohol solvent used in step a) include, but are not limited to methanol, ethanol, isopropyl alcohol, n-butanol, tertiary butanol, 1-propanol or the like. The temperature at which the above steps may be carried out in between about 10 °C and about 100 °C, based on the solvent or mixture of solvent used in particular step. The isolation of step b) can be effected, if desired, by any suitable separation methods such as precipitation, filtration, centrifugation, extraction, acid-base treatment, conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures. In the fifth aspect, the present invention provides a crystalline form AH3 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 8.2, 18.3 ± 0.2° 2?. In an embodiment, the application provides a crystalline form AH3 of Asciminib hydrochloride, characterized by a PXRD having additional peak at about 6.8, 10.8 and 13.3 ± 0.2° 2?. In an embodiment, the present application provides crystalline form AH3 of Asciminib hydrochloride, characterized by a PXRD substantially as shown in Figure 3. In the sixth aspect, the present invention provides a process for preparation of crystalline form AH3 of Asciminib hydrochloride, comprising; a) providing a mixture of Asciminib in alcoholic hydrochloride; b) isolating crystalline form AH3 of Asciminib hydrochloride. In embodiments of step a) involves the solution may optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable material to remove color and/or to clarify the solution. Suitable alcoholic hydrochloride used in step a) include, but are not limited to methanolic hydrochloride, ethanolic hydrochloride, isopropyl alcohol hydrochloride, n-butanol hydrochloride, 1-propanol hydrochloride or the like. The temperature at which the above steps may be carried out in between DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 7 about 10 °C and about 100 °C, based on the solvent or mixture of solvent used in particular step. The isolation of step b) can be effected, if desired, by any suitable separation methods such as precipitation, filtration, centrifugation, extraction, acid-base treatment, conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures. In the seventh aspect, the present application provides a pharmaceutical composition comprising crystalline Form of Asciminib hydrochloride selected from the group comprising Form AH1, Form AH2 and Form AH3 or mixtures thereof together with at least one pharmaceutically acceptable excipient. Drying in the embodiments of the present invention may be suitably carried out by using any of an air tray dryer, vacuum tray dryer, fluidized bed dryer, spin flash dryer, flash dryer, and the like. The drying may be carried out at atmospheric pressure or above, or under reduced pressures, specifically at temperatures less than about 80 °C and more specifically less than about 60 °C. The drying may be carried out for any time period required for obtaining a desired product quality, such as from about 30 minutes to about 24 hours, or longer. All PXRD data reported herein are obtained using a PANalytical X-ray Diffractometer and Bruker D8 advance X-ray Diffractometer with copper Ka radiation. Starting material may be either in a crystalline or amorphous state or an alternate crystalline form of Asciminib or Asciminib hydrochloride known in the literature. Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application. DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 8 Definitions The term "about" when used in the present application preceding a number and referring to it, is meant to designate any value which lies within the range of ±10%, preferably within a range of ±5%, more preferably within a range of ±2%, still more preferably within a range of ±1 % of its value. For example "about 10" should be construed as meaning within the range of 9 to 11, preferably within the range of 9.5 to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably within the range of 9.9 to 10.1. EXAMPLES Example-1: Preparation of crystalline form AH1 of Asciminib hydrochloride. Asciminib (100 mg), Sulfolane (0.1 mL) and aqueous HCl (45 µL) were taken in a mortar and ground the mixture using pestle for 15 minutes. Methyl tertiary butyl ether (3 mL) was added to the resultant mass and further ground for 5 minutes using pestle to obtain the title compound. PXRD: Crystalline Form AH1 of Asciminib hydrochloride (Figure 1). Example-2: Preparation of crystalline form AH2 of Asciminib hydrochloride. Amorphous Asciminib hydrochloride (400 mg) was added to the tert-butanol (2 mL) at 30 °C and stirred for 60 minutes. The obtained reaction mass was filtered and washed with n-hexane (5 mL) and kept under drying in vacuum tray drier at 45 °C for 3-4 hours to obtain the title compound. PXRD: Crystalline Form AH2 of Asciminib hydrochloride (Figure 2). Example-3: Preparation of crystalline form AH3 of Asciminib hydrochloride. Asciminib (500 mg) was added to the isopropyl alcohol hydrochloride (3 mL) at 30 °C and stirred for 3-4 hours. The obtained reaction mass was filtered and washed with n-hexane (5 mL) and kept under suction for 10 minutes to obtain DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 9 the title compound. PXRD: Crystalline Form AH3 of Asciminib hydrochloride (Figure 3). ,CLAIMS:1) A crystalline form AH1 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 4.8, 9.7, 15.2, 16.9 and 27.3 ± 0.2° 2?. 2) A process for the preparation of a process for preparation of crystalline form AH1 of Asciminib hydrochloride, comprising; a) grinding or contacting Asciminib free base in Sulfolane solvent; b) adding aqueous hydrochloride to the mixture of step a); c) isolating crystalline form AH1 of Asciminib hydrochloride. 3) A crystalline form AH2 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 4.9, 10.8, 13.2, 15.2, 18.3 and 21.4 ± 0.2° 2?. 4) A process for preparation of crystalline form AH2 of Asciminib hydrochloride, comprising; a) providing a mixture of Asciminib hydrochloride in alcohol solvent; b) isolating crystalline form AH2 of Asciminib hydrochloride. 5) The process of claim 4, wherein alcohol solvent is selected from the group comprising of methanol, ethanol, isopropyl alcohol, n-butanol, tertiary butanol, 1-propanol. 6) A crystalline form AH3 of Asciminib hydrochloride, characterized by a PXRD comprising the peaks at about 6.8, 8,2, 10.8, 13.3 and 18.3 ± 0.2° 2?. 7) A process for preparation of crystalline form AH3 of Asciminib hydrochloride, comprising; a) providing a mixture of Asciminib in alcoholic hydrochloride; b) isolating crystalline form AH3 of Asciminib hydrochloride. DocuSign Envelope ID: 1151CE8D-94C0-40DB-B16D-2443B837ED58 11 8) The process of claim 7, wherein alcoholic hydrochloride is selected from the group comprising of methanolic hydrochloride, ethanolic hydrochloride, isopropyl alcohol hydrochloride, n-butanol hydrochloride, 1-propanol hydrochloride.