Solid state forms of (s)-(2-(5-chloro-4-methyl-1h-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2h-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride and processes for preparation thereof

Abstract

The present invention provides solid state forms of (S) - (2 - ( 5 – chloro – 4 – methyl - 1Hbenzo [d] imidazole – 2 -yl) - 2- methyl pyrrolidin - 1- yl) (5- methoxy-2- (2H -1,2,3- triazol- 2-yl) phenyl) methanone hydrochloride represented by the following structural formula-1a and processes for preparation thereof.

Description

[0001] Solid state forms of (S)-(2-(5-chloro-4-methyl-lH-benzord1imidazol-2-yl)-2- methylpyrrolidin-l-yl)(5-methoxy-2-(2H-l,2,3-triazol-2-yl)phenyl)methanone hydrochloride and processes for preparation thereof

[0002] Related applications:

[0003] This application claims the benefit of priority of our Indian patent application IN202441043737 filed on Jun 06, 2024 which is incorporated herein by reference.

[0004] Field of the Invention:

[0005] The present invention provides solid state forms of (S)-(2-(5-chloro-4-methyl-lH- benzo[d]imidazol-2-yl)-2-methylpyrrolidin- 1 -yl)(5-methoxy-2-(2H- 1 ,2,3-triazol-2-yl)phenyl) methanone hydrochloride represented by the following structural formula- la and processes for preparation thereof.

[0006] Formula- la

[0007] Background of the Invention:

[0008] (S)-(2-(5-Chloro-4-methyl-lH-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-l-yl)(5- methoxy-2-(2H-l,2,3-triazol-2-yl)phenyl)methanone hydrochloride is also known as Daridorexant Hydrochloride. It is originated by Actelion Pharmaceuticals and further developed by Idorsia Pharmaceuticals Ltd.

[0009] Daridorexant HC1 is an orexin receptor antagonist. It is approved by USFDA under the brand name QUVIVIQ, and is indicated for the treatment of adult patients with insomnia.

[0010] US9732075 describes Daridorexant, its salts and process for preparation thereof.

[0011] US9790208 describes crystalline Form 1 of Daridorexant hydrochloride and amorphous form of Daridorexant free base. Still, there is a need to develop novel solid state forms of Daridorexant hydrochloride and its processes which are viable in large scale and useful for the preparation of various pharmaceutical compositions.

[0012] The present invention provides novel solid state forms of Daridorexant hydrochloride and processes for preparation thereof.

[0013] The solid state forms of Daridorexant hydrochloride of the present invention are useful for the preparation of various pharmaceutical compositions.

[0014] Brief Description of the Invention:

[0015] The first embodiment of the present invention is to provide amorphous form of Daridorexant hydrochloride.

[0016] The second embodiment of the present invention is to provide a process for the preparation of amorphous form of Daridorexant hydrochloride.

[0017] The third embodiment of the present invention is to provide amorphous solid dispersion comprising Daridorexant hydrochloride and one or more pharmaceutically acceptable excipients.

[0018] The fourth embodiment of the present invention is to provide a process for the preparation of amorphous solid dispersion comprising Daridorexant hydrochloride and one or more pharmaceutically acceptable excipients.

[0019] Brief Description of the Drawings:

[0020] Figure- 1: Illustrates the PXRD (Powder X-Ray Diffraction) pattern of amorphous form of Daridorexant HC1, as obtained in Example -1.

[0021] Figure-2: Illustrates the PXRD pattern of amorphous solid dispersion comprising

[0022] Daridorexant HC1 and HPMC AS, as obtained in Example -2.

[0023] Figure-3: Illustrates the PXRD pattern of amorphous solid dispersion comprising

[0024] Daridorexant HC1 and HPMC HP50, as obtained in Example -3.

[0025] Figure-4: Illustrates the PXRD pattern of amorphous solid dispersion comprising

[0026] Daridorexant HC1 and povidone, as obtained in Example -4.

[0027] Figure-5: Illustrates the PXRD pattern of amorphous solid dispersion comprising

[0028] Daridorexant HC1 and Pharmacoat 645, as obtained in Example -5. Figure-6: Illustrates the PXRD (Powder X-Ray Diffraction) pattern of amorphous form of Daridorexant HC1 as obtained in Example -6.

[0029] Figure-7: Illustrates the PXRD (Powder X-Ray Diffraction) pattern of amorphous form of Daridorexant HC1, as obtained in Example -7.

[0030] Detailed Description of the Invention:

[0031] The first embodiment of the present invention provides an amorphous form of Daridorexant HC1.

[0032] The amorphous form of Daridorexant HC1 of the present invention is characterized by its PXRD pattern as shown in Figures -1, 6 & 7.

[0033] In an aspect of the first embodiment, the amorphous form of Daridorexant HC1 of the present invention is stable.

[0034] In an aspect of the first embodiment, the amorphous form of Daridorexant HC1 of the present invention is stable at 25-30°C.

[0035] In an aspect of the first embodiment, the amorphous form of Daridorexant HC1 of the present invention is stable at 25-30°C for a period of about 12 months.

[0036] The second embodiment of the present invention provides a process for the preparation of amorphous form of Daridorexant HC1, comprising; a) providing a solution of Daridorexant HC1 in a solvent or mixture of solvents, b) obtaining amorphous form of Daridorexant HC1.

[0037] The solvent can be selected from but not limited to methanol, dichloromethane or mixtures thereof.

[0038] The solution in step-a) can be provided in different ways.

[0039] In one aspect of the second embodiment of the present invention, the solution can be provided by dissolving Daridorexant HC1 in a solvent or mixture of solvents.

[0040] In another aspect of the second embodiment of the present invention, the solution can be provided by reacting Daridorexant with HC1 or a source of HC1 in presence of a solvent or mixture of solvents. In another aspect of the second embodiment of the present invention, the solution can be provided by a process in which Daridorexant HC1 is synthesized.

[0041] In another aspect of the second embodiment of the present invention provides a process for the preparation of an amorphous form of Daridorexant HC1, comprising; a) dissolving Daridorexant HC1 in a mixture of methanol and dichloromethane, b) distilling off the solvent from the solution to provide amorphous form of Daridorexant HC1.

[0042] In another aspect of the second embodiment of the present invention, Daridorexant hydrochloride is dissolved in a mixture of methanol and dichloromethane. Spray drying the obtained solution at suitable temperature to obtained the amorphous form of Daridorexant hydrochloride.

[0043] In another aspect of the second embodiment of the present invention, the process for the preparation of Daridorexant hydrochloride comprising; a) providing a solution of Daridorexant HC1 in methanol, dichloromethane or mixtures thereof, b) stirring the reaction mixture, c) filtering the reaction mixture, d) spray drying the filtrate obtained in step-c) to obtain amorphous form of Daridorexant HC1.

[0044] The third embodiment of the present invention provides an amorphous solid dispersion comprising Daridorexant HC1 and one or more pharmaceutically acceptable excipients.

[0045] The “excipient” can be selected from but not limited to polyvinylpyrrolidone (povidone or PVP), polyvinylpolypyrrolidone, polysorbate, syloid, eudragit, copovidone, cross linked polyvinyl pyrrolidone (crospovidone), polyethylene glycol (macrogol or PEG), polyvinyl alcohol, polyvinyl chloride, polyvinyl acetate, propylene glycol, cellulose, cellulose acetate phthalate (CAP), methyl cellulose, carboxymethyl cellulose (CMC, its sodium and calcium salts), carboxymethylethyl cellulose (CMEC), ethyl cellulose, hydroxymethyl cellulose, ethyl hydroxyethyl cellulose, hydroxyethylcellulose, hydroxypropyl cellulose (HPC), hydroxypropyl cellulose acetate succinate, hydroxypropyl methyl cellulose (hypromellose or HPMC), hydroxypropyl methylcellulose acetate succinate (HPMC AS), HPMC HP50, HPMC E3, HPMC E5, hydroxyethyl methyl cellulose succinate (HEMCS), hydroxypropyl cellulose acetate succinate (HPCAS), hydroxypropyl methylcellulose phthalate (HPMC-P), hydroxypropyl methylcellulose acetate phthalate, microcrystalline cellulose (MCC), cross linked sodium carboxymethyl cellulose (croscarmellose sodium), cross linked calcium carboxymethyl cellulose, magnesium stearate, aluminium stearate, calcium stearate, magnesium carbonate, talc, iron oxide (red, yellow, black), stearic acid, dextrates, dextrin, dextrose, sucrose, glucose, xylitol, lactitol, sorbitol, mannitol, maltitol, maltose, raffinose, fructose, maltodextrin, anhydrous lactose, lactose monohydrate, starches such as maize starch or corn starch, sodium starch glycolate, sodium carboxymethyl starch, pregelatinized starch, gelatin, sodium dodecyl sulfate, edetate disodium, sodium phosphate, sodium lauryl sulfate, triacetin, sucralose, calcium phosphate, polydextrose, a-, P-, y-cyclodextrins, sulfobutylether beta-cyclodextrin, sodium stearyl fumarate, fumaric acid, alginic acid, sodium alginate, propylene glycol alginate, citric acid, succinic acid, carbomer, docusate sodium, glyceryl behenate, glyceryl stearate, meglumine, arginine, polyethylene oxide, polyvinyl acetate phthalates, pharmacoat, pharmacoat 645 and the like.

[0046] In an aspect of the third embodiment of the present invention, the excipient can be selected from but not limited to HPMC AS, HPMC HP50, povidone and Pharmacoat 645.

[0047] In an aspect of third embodiment of the present invention provides an amorphous solid dispersion comprising Daridorexant HC1 and HPMC AS.

[0048] In another aspect of the third embodiment of the present invention, amorphous solid dispersion comprising Daridorexant HC1 and HPMC AS of the present invention is stable.

[0049] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and HPMC AS is stable at 25-30°C.

[0050] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and HPMC AS of the present invention is stable at 25-30°C for a period of about 12 months. In an aspect of the third embodiment of the present invention provides an amorphous solid dispersion comprising Daridorexant HC1 and HPMC HP50.

[0051] In another aspect of third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and HPMC HP50 of the present invention is stable.

[0052] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and HPMC HP50 is stable at 25-30°C.

[0053] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and HPMC HP50 of the present invention is stable at 25-30°C for a period of about 12 months.

[0054] In an aspect of the third embodiment of the present invention provides an amorphous solid dispersion comprising Daridorexant HC1 and povidone.

[0055] In another aspect of third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and povidone of the present invention is stable.

[0056] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and povidone is stable at 25-30°C.

[0057] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and povidone of the present invention is stable at 25- 30°C for a period of about 12 months.

[0058] In an aspect of the third embodiment of the present invention provides an amorphous solid dispersion comprising Daridorexant HC1 and Pharmacoat 645.

[0059] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and Pharmacoat 645 is stable.

[0060] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and Pharmacoat 645 is stable at 25-30°C.

[0061] In another aspect of the third embodiment of the present invention, the amorphous solid dispersion comprising Daridorexant HC1 and Pharmacoat 645 of the present invention is stable at 25-30°C for a period of about 12 months. The amorphous form of Daridorexant hydrochloride is stable at stress conditions like i. under 10 ton pressure; ii. thermal analysis (at 60 + 2°C) for 24 hrs; iii. under UV light (at 254 nm) for 24 hrs; iv. hygroscopicity analysis(80 RH) for 24 hrs ; drying at 60°C in vacuum tray drier and air tray drier; open conditions; water slurry at 25-30°C; grinding a sample with motor pestle.

[0062] In an aspect of the present invention, the weight ratio of the Daridorexant HC1 to the excipient(s) in the solid dispersion can be selected from about 1:0.05, about 1:0.1, about 1:0.2, about 1:0.3, about 1:0.4, about 1:0.5, about 1:0.6, about 1:0.7, about 1:0.8, about 1:0.9, about 1:1.0, about 1:1.5, about 1:2.0, about 1:2.5, about 1:3.0, about 1:3.5, about 1:4.0, about 1:4.5 or about 1:5 or any other suitable weight ratio falling between thereof.

[0063] The fourth embodiment of the present invention provides a process for the preparation of an amorphous solid dispersion comprising Daridorexant HC1 and one or more pharmaceutically acceptable excipients, comprising; a) providing a solution of Daridorexant HC1 and an excipient in a solvent or mixture of solvents, b) obtaining amorphous solid dispersion comprising Daridorexant HC1 and corresponding excipient; wherein the excipient in step-a) can be selected from those as defined above in second embodiment of the present invention.

[0064] In one aspect of the fourth embodiment of the present invention, the excipient can be selected from HPMC AS, HPMC HP50, povidone and Pharmacoat 645.

[0065] The solvent can be selected from methanol, dichloromethane or mixtures thereof.

[0066] Providing a solution of Daridorexant HC1 and an excipient in a solvent or mixture of solvents can be done in various methods.

[0067] In one aspect of the present invention, it can be carried out by dissolving Daridorexant HC1 and the excipient in a solvent or mixture of solvents. In another aspect of the present invention, it can be carried out by dissolving Daridorexant HC1 in a first solvent, dissolving the excipient in a second solvent and combining both the solutions.

[0068] In another aspect of the present invention, it can be carried out by dissolving Daridorexant HC1 in a first solvent, adding the excipient and optionally adding the second solvent to the solution.

[0069] The first solvent and the second solvent can be selected from methanol, dichloromethane or mixtures thereof.

[0070] The solution(s) obtained can be filtered optionally to make it particle free.

[0071] Obtaining amorphous form of Daridorexant HC1 and amorphous solid dispersion comprising Daridorexant HC1 and an excipient in the above processes described in the present invention can be carried out by removal of the solvent from the solution.

[0072] The technique that can be used for the removal of solvent from the solution can be distillation optionally under reduced pressure.

[0073] V arious techniques that can be used for the removal of solvent can be selected from but not limited to filtration optionally under reduced pressure, cooling the solution followed by filtration, evaporation, distillation under reduced pressure, combining the solution with a suitable second solvent and filtering the solid optionally under reduced pressure, spray-drying, freeze-drying or lyophilization and the like.

[0074] The term "spray drying" broadly refers to processes involving breaking up liquid mixtures into small droplets (atomization) and rapidly removing solvent from the mixture. In a typical spray drying apparatus, there is a strong driving force for evaporation of solvent from the droplets, which may be provided by providing a drying gas. Spray drying processes and equipment are described, for example, in Perry's Chemical Engineer's Handbook, pages. 20- 54 to 20-57 (Sixth Edition 1984).

[0075] The solid residue obtained after the solvent removal is isolated and, if desired, can be dried further using conventional methods. The advantages of the process include simplicity, eco-friendliness and suitability for commercial use. By way of non- limiting example, a typical spray drying apparatus comprises a drying chamber, atomizing means for atomizing a solvent-containing feed into the drying chamber, a source of drying gas that flows into the drying chamber to remove solvent from the atomized- solvent-containing feed, an outlet for the products of drying, and product collection means located downstream of the drying chamber. Examples of such apparatuses include Niro Models PSD-I, PSD-2 and PSD-4 (Niro AJS, Soeborg, Denmark).

[0076] Typically, the product collection means, collecting the product utilizing a cyclone connected to the drying apparatus. In the cyclone, the particles produced during spray drying are separated from the drying gas and evaporated solvent, allowing the particles to be collected. A filter may also be used to separate and collect the particles produced by spray drying.

[0077] Daridorexant and Daridorexant HC1 which are used as input in the present invention can be synthesized by any of the processes known in the art for example, by the processes as described in US9732075.

[0078] Daridorexant, Daridorexant HC1 and the excipients which are used as inputs in the processes of the present invention can be in the form of crystalline or amorphous.

[0079] The solid state forms of compound of formula- la of the present invention are useful for the preparation of various pharmaceutical compositions formulated in a manner suitable for the route of administration to be used where at least a portion of compound of formula- 1 a is present in the composition in at least one polymorphic form mentioned.

[0080] The fifth embodiment of the present invention provides the use of amorphous form of compound of formula- la of the present invention for the preparation of pharmaceutical formulations.

[0081] The sixth embodiment of the present invention provides the use of amorphous solid dispersion of compound of formula- la of the present invention for the preparation of pharmaceutical formulations. The seventh embodiment of the present invention provides a pharmaceutical composition comprising amorphous form of compound of formula- la of the present invention and at least one pharmaceutically acceptable excipient.

[0082] The eighth embodiment of the present invention provides a pharmaceutical composition comprising an amorphous solid dispersion of compound of formula- la of the present invention and at least one pharmaceutically acceptable excipient.

[0083] The ninth embodiment of the present invention provides a method of treating a patient in need thereof comprising administering to the said patient a therapeutically effective amount of amorphous form of compound of formula- la of the present invention.

[0084] The tenth embodiment of the present invention provides a method of treating a patient in need thereof comprising administering to the said patient a therapeutically effective amount of amorphous solid dispersions of the present invention.

[0085] The amorphous form of compound of formula- la produced by the process of the present invention is having particle size distribution of D90 less than about 400 pm, preferably less than about 300 pm, more preferably less than about 200 pm.

[0086] In one aspect of the present invention, the amorphous form of compound of formula- la is having particle size distribution of D90 less than about 100 pm, preferably less than about 50 pm.

[0087] The aforesaid amorphous solid dispersions of compound of formula- la produced by the processes of the present invention are having particle size distribution of D90 less than about 400 pm, preferably less than about 300 pm, more preferably less than about 200 pm.

[0088] In one aspect of the present invention, the amorphous solid dispersions of compound of formula- la are having particle size distribution of D90 less than about 100 pm, preferably less than about 50 pm. The compound of formula- la produced by various processes of the present invention can be further micronized or milled to get desired particle size to achieve desired solubility profile based on different forms of pharmaceutical composition requirements. Techniques that may be used for particle size reduction includes but not limited to single or multi-stage micronization using cutting mills, pin / cage mills, hammer mills, jet mills, fluidized bed jet mills, ball mills and roller mills. Milling / micronization may be performed before drying or after drying of the product.

[0089] P-XRD Method of Analysis:

[0090] PXRD analysis was carried out by using BRUKER / D8 ADVANCE diffractometer using CuKa radiation of wavelength 1.5406A0and at a continuous scan speed of 0.03° / min.

[0091] The best mode of carrying out the present invention is illustrated by the below mentioned examples. These examples are provided as illustration only and hence should not be construed as limitation to the scope of the invention.

[0092] Examples:

[0093] Example-1: Preparation of amorphous form of Daridorexant HC1 (Formula-la)

[0094] A mixture of methanol and dichloromethane (40 ml; 1: 1) was added to Daridorexant HC1 (1 gm) at 25-30°C and stirred for 20 min at the same temperature. Filtered the solution to make it particle free. The filtrate was heated to 45-50°C. Distilled off the solvent from the filtrate under reduced pressure and dried the obtained solid to get the title compound.

[0095] The PXRD pattern of the obtained compound is shown in Figure- 1. Yield: 647 mg.

[0096] Example-2: Preparation of amorphous solid dispersion comprising Daridorexant HC1 and HPMC AS

[0097] A mixture of methanol and dichloromethane (40 ml; 1:1) was added to a mixture of Daridorexant HC1 (1 gm) and HPMC AS (1 gm) at 25-30°C and stirred the mixture for 30 min at the same temperature. Filtered the solution to make it particle free. Heated the filtrate to 45- 50°C and stirred for 10 min at the same temperature. Distilled off the solvent from the filtrate under reduced pressure and dried the obtained solid to get the title compound.

[0098] The PXRD pattern of the obtained compound is shown in Figure-2. Yield: 1.62 gm.

[0099] Example-3: Preparation of amorphous solid dispersion comprising Daridorexant HC1 and HPMC HP50

[0100] A mixture of methanol and dichloromethane (40 ml; 1:1) was added to a mixture of Daridorexant HC1 (1 gm) and HPMC HP50 (1 gm) at 25-30°C and stirred for 30 min at the same temperature. Filtered the solution to make it particle free. Heated the filtrate to 45-50°C. Distilled off the solvent from the filtrate under reduced pressure and dried the obtained solid to get the title compound.

[0101] The PXRD pattern of the obtained compound is shown in Figure-3. Yield: 1.78 gm.

[0102] Example-4: Preparation of amorphous solid dispersion comprising Daridorexant HC1 and povidone

[0103] A mixture of methanol and dichloromethane (40 ml; 1:1) was added to a mixture of Daridorexant HC1 (1 gm) and povidone (1 gm) at 25-30°C and stirred the mixture for 20 min at the same temperature. Filtered the solution to make it particle free. Heated the filtrate to 45- 50°C. Distilled off the solvent from the filtrate under reduced pressure and dried the obtained solid to get the title compound.

[0104] The PXRD pattern of the obtained compound is shown in Figure-4. Yield: 1.68 gm.

[0105] Example-5: Preparation of amorphous solid dispersion comprising Daridorexant HC1 and Pharmacoat 645

[0106] A mixture of methanol and dichloromethane (40 ml; 1:1) was added to a mixture of Daridorexant HC1 (1 gm) and Pharmacoat 645 (1 gm) at 25-30°C and stirred the mixture for 40 min at the same temperature. Filtered the solution to make it particle free. Heated the filtrate to 45-50°C. Distilled off the solvent from the filtrate under reduced pressure and dried the obtained solid to get the title compound.

[0107] The PXRD pattern of the obtained compound is shown in Figure-5. Yield: 1.82 gm. Example-6: Preparation of amorphous form of Daridorexant HC1 (Formula-la)

[0108] A mixture of methanol and dichloromethane (200 ml; 1: 1) was added to Daridorexant HC1 (5 gm) at 25-32°C and stirred for 20 min at the same temperature. Filtered the solution to make it particle free. The filtrate was heated to 45-50°C. Distilled off the solvent from the filtrate under reduced pressure and dried the obtained solid to get the title compound. The PXRD pattern of the obtained compound is shown in Figure-6. Yield: 3.23 gm.

[0109] Example-7: Preparation of amorphous form of Daridorexant HC1 by spray drying process

[0110] Daridorexant hydrochloride (20 gm) is added to a mixture of methanol and dichloromethane (800 ml; 1: 1) at 25-30°C, stirred for 25 min at the same temperature and filtered the obtained solution to get particle free. The obtained filtrate was spray dried at below mentioned parameters to obtain amorphous form of Daridorexant hydrochloride.

[0111] Operation parameters:

[0112] Labultima Instrument;

[0113] Aspirator flow rate: 70 NM3 / hr;

[0114] Feed Rate: 8 ml / min;

[0115] Inlet temperature: 50°C to 55°C;

[0116] Gas flow N2 : 2 kg / CM2

[0117] The PXRD pattern of the obtained compound is shown in Figure-7. Yield: 15 gm

Claims

I / We claim:

1. An amorphous form of Daridorexant hydrochloride.

2. The amorphous form of Daridorexant hydrochloride as claimed in claim 1, characterized by PXRD pattern which is selected from either of figure- 1, figure-6 and figure -7.

3. Amorphous solid dispersions comprising Daridorexant hydrochloride and one or more pharmaceutically acceptable excipients.

4. The amorphous solid dispersion as claimed in claim 3, wherein the pharmaceutically acceptable excipient is selected from polyvinylpyrrolidone (povidone or PVP), polyvinylpolypyrrolidone, polysorbate, syloid, eudragit, copovidone, cross linked polyvinyl pyrrolidone (crospovidone), polyethylene glycol (macrogol or PEG), polyvinyl alcohol, polyvinyl chloride, polyvinyl acetate, propylene glycol, cellulose, cellulose acetate phthalate (CAP), methyl cellulose, carboxymethyl cellulose (CMC, its sodium and calcium salts), carboxymethylethyl cellulose (CMEC), ethyl cellulose, hydroxymethyl cellulose, ethyl hydroxyethyl cellulose, hydroxyethylcellulose, hydroxypropyl cellulose (HPC), hydroxypropyl cellulose acetate succinate, hydroxypropyl methyl cellulose (hypromellose or HPMC), hydroxypropyl methylcellulose acetate succinate (HPMC AS), HPMC HP50, HPMC E3, HPMC E5, hydroxy ethyl methyl cellulose succinate (HEMCS), hydroxypropyl cellulose acetate succinate (HPCAS), hydroxypropyl methylcellulose phthalate (HPMC-P), hydroxypropyl methylcellulose acetate phthalate, microcrystalline cellulose (MCC), cross linked sodium carboxymethyl cellulose (croscarmellose sodium), cross linked calcium carboxymethyl cellulose, magnesium stearate, aluminium stearate, calcium stearate, magnesium carbonate, talc, iron oxide (red, yellow, black), stearic acid, dextrates, dextrin, dextrose, sucrose, glucose, xylitol, lactitol, sorbitol, mannitol, maltitol, maltose, raffinose, fructose, maltodextrin, anhydrous lactose, lactose monohydrate, starches such as maize starch or com starch, sodium starch glycolate, sodium carboxymethyl starch, pregelatinized starch, gelatin, sodium dodecyl sulfate, edetate disodium, sodium phosphate, sodium lauryl sulfate, triacetin, sucralose, calcium phosphate, polydextrose, a-, P-, y-cyclodextrins, sulfobutylether beta-cyclodextrin, sodium stearyl fumarate, fumaric acid, alginic acid, sodium alginate, propylene glycol alginate, citric acid, succinic acid, carbomer, docusate sodium, glyceryl behenate, glyceryl stearate, meglumine, arginine, polyethylene oxide, polyvinyl acetate phthalates, pharmacoat, pharmacoat 645.

5. The amorphous solid dispersion as claimed in claim 3, wherein the excipient is selected from HPMC AS, HPMC HP50, povidone and Pharmacoat 645.

6. A process for the preparation of amorphous form of Daridorexant hydrochloride comprising; a) providing a solution of Daridorexant HC1 in a solvent or mixture of solvents, b) obtaining amorphous form of Daridorexant HC1.

7. The process as claimed in claim 6, wherein the solvent is selected from methanol, dichloromethane or mixtures thereof.

8. The process as claimed in claim 6, obtaining amorphous form of Daridorexant HC1 is carried out by removal of the solvent from the solution.

9. The process as claimed in claim 8, wherein the technique that is used for the removal of the solvent is selected from filtration optionally under reduced pressure, cooling the solution followed by filtration, evaporation, distillation under reduced pressure, combining the solution with a suitable second solvent and filtering the solid optionally under reduced pressure, spray-drying, freeze-drying or lyophilization.

10. The process as claimed in claim 9, wherein the technique used for the removal of solvent is distillation under reduced pressure.

11. The process as claimed in claim 10, wherein amorphous form of Daridorexant HC1 obtained is characterized by PXRD pattern as depicted in figure- 1 or figure-6.

12. The process as claimed in claim 9, wherein the technique used for the removal of solvent is spray drying.

13. The process as claimed in claim 12, wherein amorphous form of Daridorexant HC1 obtained is characterized by PXRD pattern as depicted in figure-7.

14. A process for the preparation of amorphous solid dispersion comprising Daridorexant HC1 and one or more pharmaceutically acceptable excipients, comprising; a) providing a solution of Daridorexant HC1 and an excipient in a solvent or mixture of solvents, b) obtaining amorphous solid dispersion comprising Daridorexant HC1 and corresponding excipient.

15. The process claimed in claim 14, wherein solvent is selected from methanol, dichloromethane or mixtures thereof.

16. The process as claimed in claim 14, obtaining amorphous solid dispersion comprisingDaridorexant HC1 and the excipient is carried out by removal of the solvent from the solution.

17. The process as claimed in claim 14, wherein the technique that can be used for the removal of the solvent is selected from filtration optionally under reduced pressure, cooling the solution followed by filtration, evaporation, distillation optionally under reduced pressure, combining the solution with a suitable second solvent and filtering the solid optionally under reduced pressure, spray-drying, freeze-drying or lyophilization.

18. The process as claimed in claim 14, wherein the pharmaceutically acceptable excipient is selected from HPMC AS, HPMC HP50, povidone and Pharmacoat 645.

19. The amorphous Daridorexant HC1 as claimed in claim 1 or 2, which is stable.

20. The amorphous Daridorexant HC1 as claimed in claim 19, which is stable at 25-30°C.

21. The amorphous Daridorexant HC1 as claimed in claim 20, which is stable at 25-30°C when stored at this temperature for a period of 12 months.

22. The amorphous solid dispersion of Daridorexant HC1 as claimed in claims 3 to 5, which are stable.

23. The amorphous solid dispersion of Daridorexant HC1 as claimed in claim 22, which are stable at 25-30°C.

24. The amorphous solid dispersion as claimed in claim 22, which is stable at 25-30°C when stored at this temperature for a period of 12 months.

25. Use of amorphous form of Daridorexant HC1 for the preparation of pharmaceutical formulations.

26. A pharmaceutical composition comprising amorphous form of Daridorexant HC1 and at least one pharmaceutically acceptable excipient.

27. A pharmaceutical composition comprising amorphous solid dispersion of Daridorexant HC1 and at least one pharmaceutically acceptable excipient.

28. Use of amorphous solid dispersion comprising Daridorexant HC1 and at least one pharmaceutically acceptable excipient for the preparation of pharmaceutical formulations.

29. A method of treating a patient in need thereof comprising administering to the said patient a therapeutically effective amount of amorphous solid dispersion comprising Daridorexant HC1 and at least one pharmaceutically acceptable excipient.

30. The pharmaceutically acceptable excipient as claimed in any preceding claim, is selected from HPMC AS, HPMC HP50, povidone and Pharmacoat 645.

Images