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

INTRODUCTION
Aspects of the present application relates to solid forms of Deutetrabenazine, process for the preparation and pharmaceutical composition thereof. The present application also provides hydrochloride salt of Deutetrabenazine, process for the preparation and pharmaceutical composition comprising thereof.
Deutetrabenazine or d6-tetrabenazine is a deuterated analog of tetrabenazine. The drug compound having the adopted name “Deutetrabenazine” has chemical name: (RR, SS)-1, 3, 4, 6, 7, 11b-hexahydro-9, 10-di(methoxy-d3)-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-one. Deutetrabenazine is a racemic mixture containing the following structures:

RR-Deutetrabenazine SS-Deutetrabenazine
AUSTEDOTM (Deutetrabenazine) is a vesicular monoamine transporter 2 (VMAT2) inhibitor for oral administration. AUSTEDOTM was approved as oral tablets (6 mg, 9 mg, and 12 mg) by USFDA on 3 April 2017 for the treatment of chorea associated with Huntington’s disease. In August 2017 it was also approved for the treatment of tardive dyskinesia in adults.
US8524733B1 discloses Deutetrabenazine or a pharmaceutically acceptable salt thereof, method for the treatment of chronic hyperkinetic movement disorders and pharmaceutical composition thereof.
US9550780B2 discloses crystalline Form I and crystalline Form II of Deutetrabenazine.
WO2017221169A1 discloses premixes of deutetrabenazine with polyvinylpyrrolidone K-30, copovidone, talc and magnesium stearate.
The occurrence of different crystal forms, i.e., polymorphism, is a property of some compounds. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties, such as PXRD patterns, IR absorption spectra, melting points (MP), TGA curves, DSC curves, and solubilities. Polymorphs are different solids having the same molecular structure, yet having distinct physical properties when compared to other polymorphs of the same structure.
The discovery of new polymorphs and solvates of a pharmaceutical active compound provides an opportunity to improve the performance of a drug product in terms of its bioavailability or release profile in vivo, or it may have improved stability or advantageous handling properties. Polymorphism is an unpredictable property of any given compound. This subject has been reviewed in recent articles, including A. Goho, “Tricky Business,” Science News, August 21, 2004. In general, one cannot predict whether there will be more than one form for a compound, how many forms will eventually be discovered, or how to prepare any previously unidentified form.
There remains a need to provide the new polymorphic forms of Deutetrabenazine which can be used in the pharmaceutical composition.

SUMMARY OF THE INVENTION
The present application provides solid form of Deutetrabenazine and Gentisic acid, process for the preparation and pharmaceutical composition thereof.

The present application also provides hydrochloride salt of Deutetrabenazine, process for the preparation and pharmaceutical composition comprising thereof.

BRIEF DESCRIPTION OF THE DRAWING
Figure 1 illustrates a characteristic PXRD pattern of solid form of Deutetrabenazine and Gentisic acid referred to as Form SD7.

Figure 2 illustrates a characteristic PXRD pattern of hydrochloride salt of Deutetrabenazine.

DETAILED DESCRIPTION
In an aspect, the solid form of Deutetrabenazine and Gentisic acid herein designated as Form SD7, characterized by a PXRD pattern having X-ray powder diffraction peaks selected from the following at about 5.00° and 11.42°± 0.2° 2?. Form SD7 may be further characterized by X-ray powder diffraction peaks at about 20.91° and 22.96° ± 0.2° 2?.
In another aspect, the application provides solid form of Deutetrabenazine and Gentisic acid, characterized by an X-ray powder diffraction pattern as illustrated in Figure 1.
During further studies the inventors found that the solid form of Deutetrabenazine and Gentisic acid is salt of Gentisic acid salt of Deutetrabenazine.
In another aspect, the present application provides process for the preparation of Gentisic acid salt of Deutetrabenazine, comprising the steps of:
a) mixing Deutetrabenazine and Gentisic acid in acetone;
b) obtaining the Gentisic acid salt of Deutetrabenazine by grinding the mixture;
In embodiments, Deutetrabenazine and Gentisic acid were added into a clean mortar and mixture was grinded by adding acetone. The solid form was obtained as dried powder.
In embodiments of step a), any suitable solvents can also be used other than acetone. The suitable solvents can be selected from ketones, alcohols, esters, ethers, or their mixtures.
In embodiments, the obtained solid form can be dried at suitable temperature for a suitable time.
In another aspect, the hydrochloride salt of Deutetrabenazine characterized by a PXRD pattern having X-ray powder diffraction peaks selected from the following at about 6.85° and 13.67°± 0.2° 2?. The hydrochloride salt may be further characterized by X-ray powder diffraction peaks at about 14.98° and 22.16° ± 0.2° 2?.
In another aspect, the application provides the hydrochloride salt of Deutetrabenazine characterized by an X-ray powder diffraction pattern as illustrated in Figure 2.
In another aspect, the application provides a process for the preparation of the hydrochloride salt of Deutetrabenazine; comprising,
a) dissolving Deutetrabenazine in a solvent or mixture of solvents;
b) contacting the solution obtained in step a) with a source of hydrochloric acid.
c) isolating the hydrochloride salt of Deutetrabenazine.
In embodiments of step a), Deutetrabenazine can be dissolved in a solvent or mixture of solvents to provide a solution.
Suitable solvents that may be used in step a) include, but are not limited to, alcohol solvents; ketone solvents; halogenated hydrocarbon solvents; ester solvents; nitrile solvents; polar aprotic solvents; or mixtures thereof.
The dissolution temperatures may range from about 0°C to about the reflux temperature of the solvent, depending on the solvent used for dissolution, as long as a clear solution of Deutetrabenazine is obtained without affecting its quality. 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.
In an embodiments of step b), any suitable source of hydrochloric acid can be added the solution obtained in step a). The suitable source of hydrochloric acid may be Aqueous HCl, Concentrated HCl, Hydrochloric acid dissolved in an organic solvent, dry HCl gas or any other suitable source of HCl. In embodiments of step b) the HCl may be added drop-wise, lot wise in one lot or more lots or rapidly.
In embodiments, slurry obtained by the precipitation comprising hydrochloride salt of Deutetrabenazine and solvent can be maintained at any suitable temperatures, such as about -10°C to about 40°C, or about 0°C to about 35°C. In embodiments, slurry can be maintained for about 30 minutes to about 10 hours, or longer.
In embodiments, the hydrochloride salt of Deutetrabenazine can be isolated using any techniques, such as decantation, filtration by gravity or suction, centrifugation, or the solvent can be evaporated from the mass to obtain the desired product, and optionally the solid can be washed with a solvent, such as an anti-solvent or the solvent, to reduce the amount of entrained impurities.
In embodiments, the hydrochloride salt of Deutetrabenazine that is isolated can be dried at suitable temperatures, and atmospheric or reduced pressures, for about 1-50 hours, or longer, using any types of drying equipment, such as a tray dryer, vacuum oven, air oven, fluidized bed dryer, spin flash dryer, flash dryer, and the like. Drying temperatures and times will be sufficient to achieve desired product purity.
In a specific aspect the, the application provides a process for the preparation of the hydrochloride salt of Deutetrabenazine comprising,
a) dissolving Deutetrabenazine in propylene glycol;
b) adding the aqueous HCl solution to the solution obtained in step a);
c) isolating the hydrochloride salt of Deutetrabenazine.
The hydrochloride salt of Deutetrabenazine obtained from the above process can be characterized by an X-ray powder diffraction pattern as illustrated in Figure 2.
Any physical form of Deutetrabenazine may be utilized for providing the solution of Deutetrabenazine. Deutetrabenazine that may be used as the input for the process of the present invention can be obtained by the processes described in the art. For example Deutetrabenazine may be prepared by the processes described in US8524733B1, US9550780B2, WO2015084622A1, WO2011153157A2 and WO2017182916A1.
In another aspect, the present application provides a pharmaceutical composition comprising the Gentisic acid salt of Deutetrabenazine and hydrochloride salt of Deutetrabenazine as described in the present application together with at least one pharmaceutically acceptable excipient.
Pharmaceutically acceptable excipients that are useful in the present application include, but are not limited to, any one or more of: diluents such as starches, pregelatinized starches, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar, or the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methylcelluloses, pregelatinized starches, or the like; disintegrants such as starches, sodium starch glycolate, pregelatinized starches, crospovidones, croscarmellose sodium, colloidal silicon dioxide, or the like; lubricants such as stearic acid, magnesium stearate, zinc stearate, or the like; glidants such as colloidal silicon dioxide or the like; solubility or wetting enhancers such as anionic, cationic, and neutral surfactants; complex forming agents such as various grades of cyclodextrins and resins; and release rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl methacrylates, waxes, or the like. Other pharmaceutically acceptable excipients that are useful include, but are not limited to, film-formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants, or the like.
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.
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.

General description of the PXRD equipment
X-ray diffraction was measured using PANalytical X-ray diffractometer, Model: X'Pert PRO. System description: CuK-Alpha 1 wavelength= 1 .54060, voltage 45kV, current 40 mA, divergence slit=0.5°; Sample stage=Reflection-Transmission Spinner. Scan type: Continuous; Detector - X'Celerator; Measurement parameters: Start Position [°2Th.]: 3; End Position [°2Th.]: 40; Step Size [°2Th.]:0.0167; Scan Step Time [s]: 64.770.

EXAMPLES
Example-1: Preparation of solid form of Deutetrabenazine and Gentisic acid (SD7)
Deutetrabenazine (323 mg) and Gentisic acid (154 mg) were charged into a clean mortar at room temperature. Acetone (0.5 mL) was added to the mixture and grind for 5 minutes. Acetone (0.5 mL) was again added to the mixture and grind for 5 minutes. Acetone (2 mL) was added to the mixture and grind for 5 minutes. Acetone (2 mL) was again added to the mixture and grind for 5 minutes to obtain the solid form of Deutetrabenazine and Gentisic acid (SD7).
The PXRD pattern of the isolated material is represented as Figure-1.

Example-2: Preparation of hydrochloride salt of Deutetrabenazine Deutetrabenazine (200 mg) and propylene glycol (3 mL) were charged into a clean vial. The obtained slurry was heated to 85°C and continue stirring for 30 minutes. Aqueous HCl (6 mL) was added to the slurry and heated to 60°C to get clear solution. The solution was kept in refrigerator for two days. The precipitated crystals are obtained by filtration.
The PXRD pattern of the isolated material is represented as Figure-2.

Example-3: Preparation of hydrochloride salt of Deutetrabenazine
Deutetrabenazine (2 g) and propylene glycol (5 mL) were charged into a clean vial at room5 temperature. The obtained slurry was heated to 60°C and continue stirring for 30 minutes. Aqueous HCl (6 mL) was added to the slurry at 60°C to get clear solution. The precipitated crystals cooled to room temperature and stirred for 30 minutes. The product was obtained by filtration and kept for drying in vacuum tray drier at 40°C.
,CLAIMS:We Claim:
1. Crystalline form SD7 of Gentisic acid salt of Deutetrabenazine characterized by an X-ray powder diffraction pattern comprising the peak at about 5.00° and 11.42°± 0.2° 2?.

2. Crystalline form SD7 of Gentisic acid salt of Deutetrabenazine as claimed in claim 1 further characterized by an X-ray powder diffraction pattern comprising the peak at about 20.91° and 22.96° ± 0.2° 2?.

3. A process for preparing crystalline Form SD7 of Gentisic acid salt of Deutetrabenazine comprising the steps of;
a) mixing Deutetrabenazine and Gentisic acid in acetone;
b) obtaining the Gentisic acid salt of Deutetrabenazine by grinding the mixture;

4. Hydrochloride salt of Deutetrabenazine characterized by a PXRD pattern having X-ray powder diffraction peaks selected from the following at about 6.85° and 13.67°± 0.2° 2?.

5. A process for preparing hydrochloride salt of Deutetrabenazine comprising;
a) dissolving Deutetrabenazine in a solvent or mixture of solvents;
b) contacting the solution obtained in step a) with a source of hydrochloric acid.
c) isolating the hydrochloride salt of Deutetrabenazine.

6. A process for preparing hydrochloride salt of Deutetrabenazine comprising;
a) dissolving Deutetrabenazine in propylene glycol;
b) adding the aqueous HCl solution to the solution obtained in step a);
c) isolating the hydrochloride salt of Deutetrabenazine.