Salts or co-crystals and its solid-state forms of rimegepant

Abstract

The present invention relates to novel salts or co-crystals of Rimegepant, their solid-state forms, their preparative methods, and pharmaceutical compositions thereof.

Description

[0001] “SALTS OR CO-CRYSTALS AND ITS SOLID-STATE FORMS OF RIMEGEPANT” PRIORITY

[0002] This application claims the benefit under Indian Provisional Application No.(s) IN202441087015A filed on 12 November 2024 entitled “Salts or co-crystals and its solid-state forms of Rimegepant”, & IN202441105345 A filed on 31 December 2024 entitled “Salts or co-crystals and its solid-state forms of Rimegepant”, the content of which is incorporated by reference herein.

[0003] FIELD OF THE INVENTION

[0004] The present invention relates to novel salts or co-crystals of Rimegepant, their solid-state forms, their preparative methods, and pharmaceutical compositions thereof.

[0005] BACKGROUND OF THE INVENTION

[0006] Rimegepant has been approved by U.S. Food and Drug Administration (FDA) in the form of hemisulfate sesquihydrate which is a calcitonin gene-related peptide receptor antagonist and is indicated for the acute treatment of migraine with or without aura in adults and the preventative treatment of episodic migraine in adults. Rimegepant hemisulfate is marketed by Biohaven Pharmaceuticals under the brand nameNurtec ODT and is chemically known as (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9 tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-lH-imidazo[4,5-b]pyridin-l-yl)-l-piperidine-l-carboxylate hemisulfate sesquihydrate and is represented as Formula I.

[0007]

[0008] The compound Rimegepant was first described in PCT publication WO2011046997A1 and its use thereof as a Cgrp receptor antagonists.

[0009] Rimegepant Sulfate, its crystalline forms namely Form Hl.5-1, Form P22C, Form P33, Form P35 and its process for preparation thereof are described in PCT publication W02013130402A1.

[0010] Crystalline forms Rimegepant free base namely APTI-II, APTI-III and Rimegepant free base amorphous form, its process for preparation thereof are described in PCT publication W02023045608A1. Rimegepant sulfate amorphous form and amorphous solid dispersion of Rimegepant sulfate its process for preparation thereof are described in PCT publication WO2023175632A1.

[0011] Rimegepant solvates namely methyl tert-butyl ether or isopropyl ether solvates and its crystalline forms, its process for preparation thereof are described in PCT publication WO2023142857A1.

[0012] Crystalline form of Rimegepant free base namely Form N, its process for preparation thereof was described in PCT publication WO2024180562A1.

[0013] Different salts or co-crystals and their solid-state forms of an active pharmaceutical ingredient (API) may possess different properties. Such variations in the properties of different salts and solid-state forms and solvates may provide a basis for improving formulations, for example, by facilitating better processing or handling characteristics, changing the dissolution profile in a favorable direction, or improving chemical and physical stability and shelf-life. These variations in the properties of different salts or co-crystals and their solid-state forms may also offer improvements to the final dosage forms, for instance, if they serve to improve bioavailability. Different salts or co-crystals and their solid-state forms and solvates of an active pharmaceutical ingredient (API) may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to assess variations in the properties and characteristics of a solid active pharmaceutical ingredient (API).

[0014] New salts or co-crystals and their solid-state forms of an active pharmaceutical ingredient (API) can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. They can enlarge the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, improved dissolution profile, or improved shelf-life. For at least these reasons, there is a need for additional salts or co-crystals and its solid-state forms of Rimegepant, that can be used readily in pharmaceutical compositions suitable for use as therapeutics.

[0015] SUMMARY OF THE INVENTION

[0016] The present invention generally relates to novel salts or co-crystals of Rimegepant, their preparative methods and pharmaceutical compositions thereof.

[0017] In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and p-Toluenesulfonic acid.

[0018] In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and Fumaric acid. In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and Saccharin.

[0019] In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and Citric acid.

[0020] In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and DL-Malic acid.

[0021] In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and Benzoic acid.

[0022] In accordance with one embodiment, the present invention provides salt or co-crystals of Rimegepant and Phosphoric acid.

[0023] In accordance with another embodiment, the present invention provides salt or co-crystals of amorphous Rimegepant Phosphate.

[0024] In accordance with another embodiment, the present invention provides processes for preparation of salts or co-crystals of Rimegepant of the present invention.

[0025] In accordance with another embodiment, the present invention provides use of the salts or co-crystals of Rimegepant of the present invention to prepare other solid-state forms of Rimegepant.

[0026] In accordance with another embodiment, the present invention provides pharmaceutical compositions useful for oral administration comprising salts or co-crystals of Rimegepant of the present invention and one or more pharmaceutically acceptable polymer.

[0027] In accordance with another embodiment, the present invention provides use of salts or co-crystals of Rimegepant of the present disclosure for the preparation of pharmaceutical compositions and / or formulations, particularly pharmaceutical compositions or formulations for oral administration.

[0028] In accordance with another embodiment, the present invention provides use of pharmaceutical compositions or formulations of any one of salts or co-crystals of Rimegepant of the present invention for the treatment of migraine with or without aura in adults and the preventative treatment of episodic migraine in adults

[0029] BRIEF DESCRIPTION OF DRAWINGS Figure- 1 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and p-Toluenesulfonic acid Form-DCl.

[0030] Figure-2 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2.

[0031] Figure-3 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Saccharin Form-DC3.

[0032] Figure-4 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Citric acid Form-DC4.

[0033] Figure-5 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and DL-Malic acid Form-DC5.

[0034] Figure-6 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Benzoic acid Form-DC6.

[0035] Figure-7 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7.

[0036] Figure-8 is powder X-ray diffraction (PXRD) pattern of amorphous Rimegepant Phosphate.

[0037] Figure-9 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Saccharin Form-DC3a.

[0038] Figure- 10 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Saccharin Form-DC3b.

[0039] Figure- 11 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2a.

[0040] Figure-12 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2b.

[0041] Figure- 13 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2c. Figure-14 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2d.

[0042] Figure- 15 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2e.

[0043] Figure- 16 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7a.

[0044] Figure- 17 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7b.

[0045] Figure- 18 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7c.

[0046] Figure- 19 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7d.

[0047] Figure-20 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7e.

[0048] Figure-21 is powder X-ray diffraction (PXRD) pattern of salt or co-crystal of Rimegepant and Phosphoric acid DC7f.

[0049] DETAILED DESCRIPTION OF THE INVENTION

[0050] In accordance with one embodiment, the present invention provides salts or co-crystals of Rimegepant, their preparative methods and pharmaceutical compositions thereof.

[0051] In accordance with another embodiment, the present invention provides salts or co-crystals of Rimegepant particularly, Rimegepant and p-Toluenesulfonic acid, Rimegepant and Fumaric acid, Rimegepant and Saccharin, Rimegepant and Citric acid, Rimegepant and DL-Malic acid, Rimegepant and Benzoic acid, Rimegepant and Phosphoric acid, their preparative methods, and pharmaceutical compositions thereof.

[0052] In accordance with another embodiment, the present invention provides salts or co-crystals of Rimegepant particularly, Rimegepant and p-Toluenesulfonic acid Form-DCl, Rimegepant and Fumaric acid Form-DC2, Rimegepant and Fumaric acid Form-DC2a, Rimegepant and Fumaric acid Form-DC2b, Rimegepant and Fumaric acid Form-DC2c, Rimegepant and Fumaric acid Form-DC2d, Rimegepant and Fumaric acid Form-DC2e, Rimegepant and Saccharin Form-DC3, Rimegepant and Saccharin Form-DC3a, Rimegepant and Saccharin Form-DC3b, Rimegepant and Citric acid Form-DC4, Rimegepant and DL-Malic acid Form-DC5, Rimegepant and Benzoic acid Form-DC6, Rimegepant and Phosphoric acid Form-DC7, Rimegepant and Phosphoric acid Form-DC7a, Rimegepant and Phosphoric acid Form-DC7b, Rimegepant and Phosphoric acid Form-DC7c, Rimegepant and Phosphoric acid Form-DC7d, Rimegepant and Phosphoric acid Form-DC7e, Rimegepant and Phosphoric acid DC7f, and amorphous Rimegepant Phosphate.

[0053] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and p-Toluenesulfonic acid.

[0054] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and p-Toluenesulfonic acid. The crystalline salt or co-crystal of Rimegepant and p-Toluenesulfonic acid Form-DCl may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 1. The crystalline salt or co-crystal of Rimegepant and p-Toluenesulfonic acid Form-DCl may be characterized by an X-ray powder diffraction pattern having peaks at 8.04, 8.8, 11.37, 12.98, 13.86, 15.24, 15.68, 15.93, 16.21, 16.61, 16.88, 18, 18.83, 20.15, 20.48, 21.01, 22.28, 22.63, 23.97, 24.89, 25.09, 26.25, 26.82 and 27.58 ± 0.2 degrees 2-theta.

[0055] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and Fumaric acid.

[0056] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Fumaric acid. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2 may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 2. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2 may be characterized by an X-ray powder diffraction pattern having peaks at 3.71, 4.51, 9.88, 11.98, 13.62, 14.98, 15.98, 16.46, 16.9, 18.16, 18.84, 19.98, 21.55, 22.72, 25.63, 26.42, 28.69 and 29.27 ± 0.2 degrees 2-theta.

[0057] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Fumaric acid. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2a may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 11. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2a may be characterized by an X-ray powder diffraction pattern having peaks at 5.28, 7.88, 11.46, 12.63, 14.72, 15.18, 15.98, 17.4, 18.41, 19.11, 19.7, 21.16, 22.71, 23.27, 24.36, 25.49 and 26.7 ± 0.2 degrees 2-theta.

[0058] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Fumaric acid. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2b may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 12. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2b may be characterized by an X-ray powder diffraction pattern having peaks at 5.66, 7.27, 7.6, 9.63, 11.42, 12.15, 13.95, 14.59, 15.13, 15.84, 17.11, 17.42, 17.96, 19.32, 19.98, 20.52, 22.02, 22.9, 23.46, 24.36, 24.76, 25.77, 27.76, 28.11, 30.16, 32.26 and 36.94 ± 0.2 degrees 2-theta.

[0059] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Fumaric acid. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2c may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 13. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2c may be characterized by an X-ray powder diffraction pattern having peaks at 8.2, 12, 13.1, 14.2, 15.4, 16.8, 18.3, 21.4, 21.6, 22.7, 23.3, 23.5, 24.2, 25.5, 26.4, 29.6, 30.9 and 37.7 ± 0.2 degrees 2-theta.

[0060] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Fumaric acid. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2d may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 14. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2d may be characterized by an X-ray powder diffraction pattern having peaks at 5.2, 10.69, 11.87, 14.3, 14.68, 15.47, 17.08, 17.47, 18.26, 23.81, 24.82 and 25.8 ± 0.2 degrees 2-theta.

[0061] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Fumaric acid. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2e may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 15. The crystalline salt or co-crystal of Rimegepant and Fumaric acid Form-DC2e may be characterized by an X-ray powder diffraction pattern having peaks at 5.75, 6.49, 9.6, 11.62, 12.06, 12.79, 13.17, 13.81, 14.53, 14.95, 15.51, 16.32, 16.67, 17.42, 18.53, 19.39, 20.76, 20.83, 21.78, 22.94, 23.59, 23.92, 24.3, 24.99, 25.92, 26.64, 27.81, 28.51, 29.01, 29.82, 30.95, 35.41, 37.09 and 39.5 ± 0.2 degrees 2-theta.

[0062] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and Saccharin. In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Saccharin. The crystalline salt or co-crystal of Rimegepant and Saccharin Form-DC3 may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 3. The crystalline salt or co-crystal of Rimegepant and Saccharin Form-DC3 may be characterized by an X-ray powder diffraction pattern having peaks at 7.53, 7.91, 8.55, 9.53, 10.77, 11.31, 12.83, 13.25, 13.9, 15.1, 15.56, 15.93, 16.71, 17.23, 17.66, 18.39, 18.82, 20.45, 20.89, 21.31, 22.87, 23.41, 24.16, 24.55, 25.02, 25.26, 25.68, 25.97, 26.71, 27.09, 27.4, 27.79, 29.09, 30.67, 31.6, 32.42, 33.01, 34.18, 36.78 and 37.6 ± 0.2 degrees 2-theta.

[0063] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Saccharin. The crystalline salt or co-crystal of Rimegepant and Saccharin Form-DC3a may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 9. The crystalline salt or co-crystal of Rimegepant and Saccharin Form-DC3a may be characterized by an X-ray powder diffraction pattern having peaks at 7.51, 8.85, 11.01, 13.6, 15.11, 15.86, 17.08, 18.92, 20.24, 21.24, 23.09, 25.49, 27.09, 30.68 and 32.74 ± 0.2 degrees 2-theta.

[0064] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Saccharin. The crystalline salt or co-crystal of Rimegepant and Saccharin Form-DC3b may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 10. The crystalline salt or co-crystal of Rimegepant and Saccharin Form-DC3b may be characterized by an X-ray powder diffraction pattern having peaks at 8.3, 9, 11.6, 12, 12.5, 13.2, 13.4, 15, 15.7, 16.2, 16.7, 17.4, 17.8, 19.2, 20.3, 20.6, 21.1, 22.2, 23.9, 24.2, 24.6, 25, 25.3, 25.9, 26.7, 27.5, 28.6, 29.4, 30 and 36.2 ± 0.2 degrees 2-theta.

[0065] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and Citric acid.

[0066] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Citric acid. The crystalline salt or co-crystal of Rimegepant and Citric acid Form-DC4 may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 4. The crystalline salt or co-crystal of Rimegepant and Citric acid Form-DC4 may be characterized by an X-ray powder diffraction pattern having peaks at 9.05, 11.41, 12.09, 12.6, 13.36, 14.61, 15.02, 15.68, 16.35, 17.62, 18.02, 18.46, 18.96, 20.45, 20.8, 21.24, 21.7, 23.44, 24.79 and 25.79± 0.2 degrees 2-theta. In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and DL-Malic acid.

[0067] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and DL-Malic acid. The crystalline salt or co-crystal of Rimegepant and DL-Malic acid Form-DC5 may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 5. The crystalline salt or co-crystal of Rimegepant and DL-Malic acid Form-DC5 may be characterized by an X-ray powder diffraction pattern having peaks at 9.07, 10.23, 11.6, 12.02, 12.53, 13.37, 14.54, 15, 15.69, 16.5, 17.78, 18.81, 19.1, 20.28, 20.61, 21.18, 22.06, 24.69, 25.39, 26.22 and 27.7± 0.2 degrees 2-theta.

[0068] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and Benzoic acid.

[0069] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Benzoic acid. The crystalline salt or co-crystal of Rimegepant and Benzoic acid Form-DC6 may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 6. The crystalline salt or co-crystal of Rimegepant and Benzoic acid Form-DC6 may be characterized by an X-ray powder diffraction pattern having peaks at 4.16, 8.24, 9, 11.53, 11.84, 12.45, 14.32, 14.85, 16.08, 16.59, 17, 18.84, 20.44, 20.71, 21.63, 21.78, 22.26, 24.3, 25.66, 26.38, 27.4 and 29.24± 0.2 degrees 2-theta.

[0070] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and Phosphoric acid.

[0071] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7 may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 15. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7 may be characterized by an X-ray powder diffraction pattern having peaks at 5.27 , 7.87 , 11.43 , 12.61 , 13.66 , 14.69 , 15.17 , 16.02 , 17.39 , 18.4 , 19.1 , 19.71 , 20.53 , 21.18 , 22.71 , 23.28 , 24.34 , 24.91 , 25.46 , 26.28 , 26.73, 27.84 , 28.78 , 30.23 , 30.78 , 32.65 , 33.35 , 34.31 , 36.6 , 37.4 and 37.84 ± 0.2 degrees 2-theta.

[0072] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7a may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figurel6. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7a may be characterized by an X-ray powder diffraction pattern having peaks at 5.8, 9.6, 11.7, 12.9, 13.2, 13.9, 14.6, 15, 16.7, 17.5, 19.5, 20.9, 23, 24.1, 28.6 and 29.9 ± 0.2 degrees 2-theta.

[0073] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7b may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 17. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7b may be characterized by an X-ray powder diffraction pattern having peaks at 5.9, 8, 8.58, 9.72, 11.94, 13.29, 15.28, 17.09, 17.79, 18.56, 19.19, 19.55, 20.96, 21.86, 23.17, 23.98 and 26.78 ± 0.2 degrees 2-theta.

[0074] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7c may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 18. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7c may be characterized by an X-ray powder diffraction pattern having peaks at 4.08, 8.29, 9.09, 10.2, 11.57, 12.68, 13.47, 14.65, 15.1, 15.77, 16.42, 17.8, 19.1, 20.44, 20.77, 21.27, 22.01, 22.75, 24.75, 25.63, 26.03, 27.63, 28.72 and 29.38 ± 0.2 degrees 2-theta.

[0075] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7d may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 19. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7d may be characterized by an X-ray powder diffraction pattern having peaks at 8.41, 9.84, 10.77, 12.01, 13.01, 14.86, 15.41, 16.12, 16.4, 16.48, 16.96, 18.47, 20.47, 21.05, 24.95 and 25.71 ± 0.2 degrees 2-theta.

[0076] In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7e may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 20. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7e may be characterized by an X-ray powder diffraction pattern having peaks at 5.69, 10.69, 11.95, 14.51, 15.36, 17.18, 18.07, 21.58, 22.26, 25.41 and 27.65 ± 0.2 degrees 2-theta. In accordance with another embodiment, the present invention provides crystalline salt or co-crystal of Rimegepant and Phosphoric acid. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7f may be characterized by an X-ray powder diffraction pattern substantially as depicted in Figure 21. The crystalline salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7f may be characterized by an X-ray powder diffraction pattern having peaks at 6.01, 6.18, 6.87, 8.65, 11, 12.12, 12.94, 13.65, 14.63, 15.91, 16.44, 16.72, 16.95, 17.22, 18.26, 19.09, 19.32, 19.73, 20.1, 20.93, 21.64, 22.54, 22.91, 25.18, 25.63, 26.39, 26.93, 27.81, 28.44, 29.98, 30.3, 30.64 and 32.29 ± 0.2 degrees 2-theta.

[0077] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7 is anhydrous mono phosphate.

[0078] In accordance with another embodiment, the present invention provides process for preparation of salt or co-crystals of amorphous Rimegepant Phosphate.

[0079] In accordance with another embodiment, the present invention provides processes for preparation of salts or co-crystals of Rimegepant of the present invention.

[0080] In accordance with another embodiment, the present invention provides salt or co-crystal of Rimegepant is a hydrate, anhydrate, or solvate.

[0081] In accordance with another embodiment, the present invention provides processes for preparation of salts or co-crystals of Rimegepant, comprising:

[0082] a) suspending or dissolving Rimegepant and a suitable salt forming agent or co-former in a suitable solvent, (OR)

[0083] suspending or dissolving salts or co-crystals of Rimegepant in a suitable solvent,

[0084] b) optionally stirring the step a) reaction mass; and

[0085] c) isolating the salt or co-crystal of Rimegepant.

[0086] The step a) of forgoing process involves, suspending or dissolving Rimegepant and a suitable salt forming agent or co-former (OR) suspending or dissolving salts or co-crystals of Rimegepant in a suitable solvent at a temperature of about 0°C to about reflux temperature.

[0087] The step b) of the process involves optionally stirring the step a) suspension or solution at a temperature of about 0°C to about reflux temperature.

[0088] Then the resultant salt or co-crystal of Rimegepant can be isolated by conventional techniques such as precipitation by cooling the reaction mass, isolated by precipitation by cooling the reaction mass, isolated by solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation, or filtration. The resultant product may optionally be further dried at a suitable temperature for a sufficient period.

[0089] In accordance with another embodiment, the present invention provides a process for preparation of salt or co-crystal of Rimegepant Phosphoric acid Form-DC7, comprising:

[0090] a) suspending or dissolving Rimegepant in a suitable solvent,

[0091] b) adding phosphoric acid to the step a) reaction mass (Or) adding the step a) reaction mass to phosphoric acid,

[0092] c) optionally stirring the step b) reaction mass;

[0093] d) optionally concentrating the reaction mass and adding a suitable solvent to the reaction mass, e) optionally stirring the step d) reaction mass; and

[0094] f) isolating the salt or co-crystal of Rimegepant.

[0095] The step a) of forgoing process involves, suspending or dissolving Rimegepant in a suitable solvent at a temperature of about 0°C to about reflux temperature.

[0096] The step b) of the process involves adding phosphoric acid to the step a) reaction mass (Or) adding the step a) reaction mass to phosphoric acid. Where in the phosphoric acid can be diluted with a suitable solvent before adding to the reaction mass.

[0097] The step b) of the process involves optionally stirring the step b) suspension or solution at a temperature of about 0°C to about reflux temperature and followed by optionally concentrating the reaction mass and adding a suitable solvent to the reaction mass. The suitable solvent used in the Step d) can be same as the solvent used on Step a) or different.

[0098] Then the resultant salt or co-crystal of Rimegepant Phosphoric acid Form-DC7 can be isolated by conventional techniques such as precipitation by cooling the reaction mass, isolated by precipitation by cooling the reaction mass, isolated by solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation, or filtration. The resultant product may optionally be further dried at a suitable temperature for a sufficient period.

[0099] Unless otherwise specified the term “suitable solvent” used herein for the above embodiments is selected from but not limited to alcohols, amides, aliphatic or alicyclic hydrocarbons, sulfoxides, ketones, nitriles, ethers, esters, halogenated hydrocarbons, aromatic hydrocarbons and the like, water and mixtures thereof. The alcohols include, but are not limited to methanol, ethanol, propanol, butanol and the like; amides include, but are not limited to dimethylacetamide, dimethylformamide, N- methylpyrrolidone and the like; aliphatic or alicyclic hydrocarbons include, but are not limited to n-pentane, isopentane, neopentane, n-hexane, isohexane, 3 -methylpentane, 2, 3 -dimethylbutane, neohexane, n-heptane, isoheptane, 3 -methylhexane, neoheptane, 2,3 -dimethylpentane, 2,4-dimethylpentane, 3, 3 -dimethylpentane, 3 -ethylpentane, 2,2, 3 -trimethylbutane, n-octane, isooctane, 3 -methylheptane, neooctane, cyclohexane, methylcyclohexane, cycloheptane, Cs-Cs aliphatic hydrocarbons, petroleum ethers and the like; sulfoxides include, but are not limited to dimethyl sulfoxide, diethyl sulfoxide and the like; ketones include, but are not limited to acetone, methyl isobutyl ketone, methyl ethyl ketone and the like; nitriles include, but are not limited to acetonitrile, propionitrile and the like; ethers include, but are not limited to tetrahydrofuran, methyl tetrahydrofuran, diethyl ether, diisopropyl ether, methyl tert-butyl ether, 1,4-di oxane and the like; esters such as methyl acetate, ethyl acetate, isobutyl acetate and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, chloroform and the like; aromatic hydrocarbons include, but are not limited to toluene, xylene and the like; water and mixture thereof. Preferably Acetone, Methanol, Isopropyl alcohol, tetrahydrofuran, Methyl tert-butyl ether, dichloromethane, Acetonitrile, Ethyl acetate, Heptane, water and mixture thereof.

[0100] Unless otherwise specified the product of the above said reaction can be isolated by any suitable conventional techniques such as precipitation by cooling the reaction mass, isolated by solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration. The resultant product may optionally be further dried at a temperature of about 25°C to about 120°C for a sufficient period. Drying can be suitably carried out in a tray dryer, vacuum oven, air oven and the like.

[0101] Unless otherwise specified the term “about” used herein 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.

[0102] In accordance with another embodiment, the present invention provides use of the salts or co-crystals of Rimegepant of the present invention to prepare other solid-state forms of Rimegepant.

[0103] In accordance with another embodiment, the present invention provides the Rimegepant salts or cocrystals, and its solid forms of the present application are stable under thermal, humid and stress conditions. In accordance with another embodiment, the present invention provides the Rimegepant salts or cocrystals, and its solid forms of the present application are stable 25±2°C / 60% RH ±5% RH and 40°C±2°C / 75% RH ±5% RH up to 3 Months.

[0104] In accordance with another embodiment, the present invention provides pharmaceutical compositions useful for oral administration comprising salts or co-crystals of Rimegepant of the present invention and one or more pharmaceutically acceptable polymer.

[0105] In accordance with another embodiment, the present invention provides use of salts or co-crystals of Rimegepant of the present disclosure for the preparation of pharmaceutical compositions and / or formulations, particularly pharmaceutical compositions or formulations for oral administration.

[0106] In accordance with another embodiment, the present invention provides use of pharmaceutical compositions or formulations of any one of salts or co-crystals of Rimegepant of the present invention for the treatment of migraine with or without aura in adults and the preventative treatment of episodic migraine in adults.

[0107] EXAMPLES

[0108] The following non-limiting examples illustrate specific embodiments of the present invention. They are not intended to limit the scope of the present invention in any way.

[0109] EXAMPLE 1: Preparation of salt or co-crystal of Rimegepant and p-Toluenesulfonic acid Form-DCl.

[0110] A slurry of Rimegepant free base (500 mg) and p-Toluenesulfonic acid (PTS A) (90 mg) in Acetone (5 mL) was stirred at room temperature for 11-12 days. The resulting solid was filtered under vacuum and dried in VTD at 29°C for about 24 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.1.

[0111] EXAMPLE 2: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DCl.

[0112] A slurry of Rimegepant free base (500 mg) and Fumaric acid (220 mg) in Acetone (5 mL) was stirred at room temperature for about 7 days. The resulting solid was filtered under vacuum and dried in VTD at 29°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.2.

[0113] EXAMPLE 3: Preparation of salt or co-crystal of Rimegepant and Saccharin Form-DC3. A slurry of Rimegepant free base (500 mg) and Saccharin (350 mg) in Acetone (5 mL) was stirred at room temperature for about 7 days. The resulting solid was filtered under vacuum and dried in VTD at 29°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.3.

[0114] EXAMPLE 3a: Preparation of salt or co-crystal of Rimegepant and Saccharin Form-DC3. Taken Rimegepant free base (10 g, Imole eqt) and Saccharin (3.38 g, Imole eqt) in Methanol (100 mL). The above solution was heated to 50°C and maintained for 60mins and cooled to -10°C in 0.1°C / min ramp and maintained for 12hrs. The resulting solid was filtered under vacuum and dried in VTD at 50°C for about 4 to 5 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.3. TGA (wt.%): 1.2 (120), 2.8 (180); DSC (°C): 134 and 210; Moisture Content: 3.42%.

[0115] EXAMPLE 4: Preparation of salt or co-crystal of Rimegepant and Citric acid Form-DC4. A slurry of Rimegepant free base (500 mg) and Citric acid (370 mg) in Acetone (5 mL) was stirred at room temperature for about 7 days. The resulting solid was filtered under vacuum and dried in VTD at 29°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.4.

[0116] EXAMPLE 5: Preparation of salt or co-crystal of Rimegepant and DL-Malic acid Form-DC5.

[0117] A slurry of Rimegepant free base (500 mg) and DL-Malic acid (125 mg) in Acetone (5 mL) was stirred at room temperature for about 7 days. The resulting solid was filtered under vacuum and dried in VTD at 29°C for about 15 to 20 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.5.

[0118] EXAMPLE 6: Preparation of salt or co-crystal of Rimegepant and Benzoic acid Form-DC6.

[0119] A slurry of Rimegepant free base (500 mg) and Benzoic acid (120 mg) in Acetone (5 mL) was stirred at room temperature for about 7 days. The resulting solid was filtered under vacuum and dried in VTD at 29°C for about 15 to 20 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.6.

[0120] EXAMPLE 7: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7.

[0121] A slurry of Rimegepant free base (500 mg) and Phosphoric acid (103 mg) in Isopropyl alcohol (5 mL) was stirred at room temperature for about 7 days. Added Phosphoric acid (50 mg) and continued slurry for about 1-2 days. The resulting solid was filtered under vacuum and dried in VTD at 50°C for about 8 hrs, at 70°C for about 20hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig.7; TGA (wt.%): 0.8; DSC: 87°C, 203°C; Moisture Content: 1.5%.

[0122] EXAMPLE 8: Preparation of salt or co-crystal of amorphous Rimegepant Phosphate.

[0123] Rimegepant free base (0.8g) and tetrahydrofuran (24mL) were added in to a round bottom flask at 25±5°C. The reaction mass temperature was raised to reflux for 10-15 min. To the reaction mass was added 85% phosphoric acid (0.337g) at reflux temperature and maintain for 10-15 min. Then the reaction mass temperature was allowed to cool to 30+5 °C and stirred for 5 hours at same temperature. Filtered the solid and washed with methyl tert-butyl ether (0.8mL><3), dried the solid at 50-55°C under vacuum. Wt: 0.82 g. PXRD: Fig. 8.

[0124] EXAMPLE 9: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7.

[0125] A solution of 85% orthophosphoric acid (259g) in isopropyl alcohol (1.2L) was slowly added to a solution of Rimegepant free base (600g) in dichloromethane (6L) at 25-35°C, resulting heterogeneous mixture was stirred at 25-35°C for 2-3 hr. Distilled out the solvent up to 1 vol and co-distilled with isopropyl alcohol. Isopropyl alcohol (6L) was added to the resulted residue and maintained for 1 hr at 50-55°C. Reaction mass was cooled to 25-35°C and maintained for 10-12 hr at 25-35°C. Thus, the resulted material was filtered and washed with isopropyl alcohol under nitrogen atmosphere. Dried the wet material at 50-55°C for 10 hr under vacuum to obtain the DC7 form of Rimegepant phosphate. Wt: 585g. PXRD: Fig.7.

[0126] EXAMPLE 10: Preparation of salt or co-crystal of Rimegepant Phosphate Form DC7.

[0127] Rimegepant free base (0.5g), tetrahydrofuran (5mL) and water (ImL) were added in to a round bottom flask at25±5°C and allowed to stir for 10-15 min. Concentrated the solvent completely under vacuum at below 50°C and chase-up with isopropyl alcohol (7mL). To the reaction mass was added 85% phosphoric acid (0.215g) and temperature raised to 50-55°C, allowed to stir for 5 hours at same temperature. Then the reaction mass temperature was allowed to cool to 30+5°C and stirred for 1 hour at same temperature. Filtered the solid and washed with Methyl tert-butyl ether (0.5mL><3), dried the solid at 50-55 °C under vacuum. Wt: 0.48 g.

[0128] EXAMPLE 11: Preparation of salt or co-crystal of Rimegepant and Saccharin Form-DC3a. A slurry of Rimegepant Saccharate (100 mg) in 2-Propanol (0.25 mL) was stirred at room temperature for about 7 days to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 1.

[0129] EXAMPLE 12: Preparation of salt or co-crystal of Rimegepant and Saccharin Form-DC3b. A slurry of Rimegepant Saccharate (100 mg) in 2-Propanol (0.25 mL) was stirred at room temperature for about 7 days to obtain the Form Dc3a. Drying the Form Dc3a in VTD at RT for 20 to 24 hrs and at 65°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 2.

[0130] EXAMPLE 13: Preparation of salt or co-crystal of Rimegepant and Saccharin FormDC3b. A slurry of Rimegepant Saccharate (100 mg) in any one of the solvent (Acetonitrile (0.25mL), or water (0.25 mL), or Ethyl acetate (0.25mL), or 1:1 mixture of 2-Propanol (0.125mL) and DM water (0.125 mL)) was stirred at room temperature for about 7 days and PXRD collected. The resulting solid was filtered under vacuum and dried in VTD at RT for 20 to 24 hrs and at 65°C for about 6 to 7 hrs to obtain the title compound. Both wet and dry provided the title compound. The PXRD of the resultant solid material is given in Fig. 2.

[0131] EXAMPLE 14: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2a.

[0132] A slurry of Rimegepant Fumarate (100 mg) in Solvent (0.25mL; 2-Propanol, or Acetonitrile, or Ethyl acetate, or Heptane) was stirred at room temperature for about 5 days, to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 3.

[0133] EXAMPLE 15: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2b.

[0134] A slurry of Rimegepant Fumarate (100 mg) in Solvent (0.25mL; water, or 1:1 mixture of water (0.125mL) and Acetone (0.125mL)) was stirred at room temperature for about 5 days, to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 4.

[0135] EXAMPLE 16: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2c.

[0136] A slurry of Rimegepant Fumarate (100 mg) in 1:1 mixture of Acetonitrile (0.125mL) and DM water (0.125 mL) was stirred at room temperature for about 5 days, to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 5.

[0137] EXAMPLE 17: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2d.

[0138] Rimegepant free base (10 grams) and Fumaric acid (2.170 g) were added to in Acetone (100 mL) and the solution was heated to 50°C and maintained for 60mins to obtain clear solution and cooled to -4C in 0.1 °C / min ramp and maintained for 2 days and further heated to room temperature, added 1.15 grams of Fumaric acid and slurry for about 4 days. The resulting solid was filtered under vacuum and dried in VTD at 50°C for about 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 6.

[0139] EXAMPLE 18: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2d.

[0140] A slurry of Rimegepant Fumarate (100 mg) in Heptane (0.25mL) was stirred at room temperature for about 5 days to obtain the DC2a, which was dried in VTD at RT for 20 to 24 hrs and at 65°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 6.

[0141] EXAMPLE 19: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2e.

[0142] A slurry of Rimegepant Fumarate (100 mg) in Acetonitrile (0.25mL) was stirred at room temperature for about 5 days to obtain DC2a, which was dried in VTD at RT for 20 to 24 hrs and at 65 °C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 7. EXAMPLE 20: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2e.

[0143] A slurry of Rimegepant Fumarate (100 mg) in solvent (water (0.25mL), or 1:1 mixture of water (0.125mL) and Acetone (0.125mL)) was stirred at room temperature for about 5 days to obtain DC2b, which was dried in VTD at RT for 20 to 24 hrs and at 65°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 7.

[0144] EXAMPLE 21: Preparation of salt or co-crystal of Rimegepant and Fumaric acid Form-DC2e.

[0145] A slurry of Rimegepant Fumarate (100 mg) in 1 : 1 mixture of Acetonitrile (0.125mL) and water (0.125 mL) was stirred at room temperature for about 5 days to obtain DC2c, which was dried in VTD at RT for 20 to 24 hrs and at 65°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 7.

[0146] EXAMPLE 22: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7a.

[0147] A slurry of Rimegepant Phosphate (100 mg) in Solvent (1:1 mix of Acetone (0.125mL) and DM water (0.125mL), or Acetonitrile (0.25mL)) was stirred at room temperature for about 5 days, to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 8.

[0148] EXAMPLE 23: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7b.

[0149] A slurry of Rimegepant Phosphate (100 mg) in solvent (1:1 ix of Acetonitrile (0.125mL) and DM water (0.125 mL), or water (0.25mL)) was stirred at room temperature for about 5 days to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 9.

[0150] EXAMPLE 24: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7c.

[0151] A slurry of Rimegepant Phosphate (100 mg) in solvent (2 -Propanol (0.25 mL), or 1:1 mix of 2-Propanol (0.125mL) and DM water (0.125 mL)) stirred at room temperature for about 5 days to obtain the wet PXRD pattern. The PXRD of the resultant solid material is given in Fig. 10.

[0152] EXAMPLE 25: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7d.

[0153] A slurry of Rimegepant Phosphate (100 mg) in solvent (Acetone, 0.25 mL) was stirred at room temperature for about 5 days to obtain wet PXRD pattern. The PXRD of the resultant solid material is given in Fig. 11.

[0154] EXAMPLE 26: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7e.

[0155] A slurry of Rimegepant Phosphate (100 mg) in solvent (Heptane, 0.25 mL) was stirred at room temperature for about 5 days to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 12. EXAMPLE 27: Preparation of salt or co-crystal of Rimegepant and Phosphoric acid Form-DC7f.

[0156] A slurry of Rimegepant Phosphate (100 mg) in water (0.25 mL) was stirred at room temperature for about 5 days to obtain DC7b. The resulting solid was filtered under vacuum and dried in VTD at RT for 20 to 24 hrs and at 65°C for about 6 to 7 hrs to obtain the title compound. The PXRD of the resultant solid material is given in Fig. 13.

[0157] EXAMPLE 28: Preparation of salt or co-crystal of Rimegepant Fumarate Form DC2d.

[0158] Rimegepant free base (2g), acetone (20mL) and Fumaric acid (0.651) were added in to a round bottom flask at 25±5°C. Reaction mass was heated to 50-55°C and maintained to 10-15 min. Then the reaction mass temperature was allowed to cool to 30+5 °C and stirred for 5 hours at same temperature. Filtered the solid and washed with Methyl tert-butyl ether (0.5mL><3), dried the solid at 50-55°C under vacuum. Wt: 1.98 g.

[0159] EXAMPLE 29: Preparation of salt or co-crystal of Rimegepant Fumarate Form DC2e.

[0160] Rimegepant fumarate DC2d (1g) and Acetonitrile (lOmL) were added in to a round bottom flask at 25±5°C. Reaction mass was heated to 50-55°C and maintained to 5 hours at same temperature. Then the reaction mass temperature was allowed to cool to 30+5°C and stirred for 1 hour at same temperature. Filtered the solid and washed with Methyl tert-butyl ether (0.5mL><3), dried the solid at 50-55°C under vacuum. Wt: 0.8 g.

[0161] It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be constructed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the present invention are for illustration purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the specification appended hereto.

Claims

What is claims:

1. A crystalline or amorphous, salt or co-crystals of Rimegepant:a) Rimegepant and p-Toluenesulfonic acid,b) Rimegepant and Fumaric acid,c) Rimegepant and Saccharin,d) Rimegepant and Citric acid,e) Rimegepant and DL-Malic acid,f) Rimegepant and Benzoic acid, andg) Rimegepant and Phosphoric acid.

2. The salt or co-crystal of Rimegepant of claim 1, wherein said salt or co-crystal is a solvate, hydrate, or anhydrate.

3. The salt or co-crystal of Rimegepant of any one of claims 1, wherein said salt or co-crystal is crystalline and is selected from the group consisting of Rimegepant and p-Toluenesulfonic acid Form-DCl, Rimegepant and Fumaric acid Form-DC2, Rimegepant and Fumaric acid Form-DC2a, Rimegepant and Fumaric acid Form-DC2b, Rimegepant and Fumaric acid Form- DC2c, Rimegepant and Fumaric acid Form-DC2d, Rimegepant and Fumaric acid Form- DC2e, Rimegepant and Saccharin Form-DC3, Rimegepant and Saccharin Form-DC3a, Rimegepant and Saccharin Form-DC3b, Rimegepant and Citric acid Form-DC4, Rimegepant and DL-Malic acid Form-DC5, Rimegepant and Benzoic acid Form-DC6, Rimegepant and Phosphoric acid Form-DC7, Rimegepant and Phosphoric acid Form-DC7a, Rimegepant and Phosphoric acid Form-DC7b, Rimegepant and Phosphoric acid Form-DC7c, Rimegepant and Phosphoric acid Form-DC7d, Rimegepant and Phosphoric acid Form-DC7e, Rimegepant and Phosphoric acid DC7f, and amorphous Rimegepant Phosphate.

4. The salt or co-crystal of claim 1, wherein the form is Rimegepant Saccharin Form-DC3, characterized by X-ray powder diffraction pattern, comprising three or more peaks selected from at 7.53, 7.91, 8.55, 9.53, 10.77, 11.31, 12.83, 13.25, 13.9, 15.1, 15.56, 15.93, 16.71, 17.23, 17.66, 18.39, 18.82, 20.45, 20.89, 21.31, 22.87, 23.41, 24.16, 24.55, 25.02, 25.26, 25.68, 25.97, 26.71, 27.09, 27.4, 27.79, 29.09, 30.67, 31.6, 32.42, 33.01, 34.18, 36.78 and 37.6 ± 0.2 degrees 2-theta.

5. The salt or co-crystal of claim 1, wherein the form is Rimegepant Saccharin Form-DC3b, characterized by X-ray powder diffraction pattern, comprising three or more peaks selectedfrom at8.3, 9, 11.6, 12, 12.5, 13.2, 13.4, 15, 15.7, 16.2, 16.7, 17.4, 17.8, 19.2, 20.3, 20.6, 21.1, 22.2, 23.9, 24.2, 24.6, 25, 25.3, 25.9, 26.7, 27.5, 28.6, 29.4, 30 and 36.2 ± 0.2 degrees 2-theta.

6. The salt or co-crystal of claim 1, wherein the form is Rimegepant Benzoic acid Form-DC6, characterized by X-ray powder diffraction pattern, comprising three or more peaks selected from at 4.16, 8.24, 9, 11.53, 11.84, 12.45, 14.32, 14.85, 16.08, 16.59, 17, 18.84, 20.44, 20.71, 21.63, 21.78, 22.26, 24.3, 25.66, 26.38, 27.4 and 29.24 ± 0.2 degrees 2-theta.

7. The salt or co-crystal of claim 1, wherein the form is Rimegepant Phosphoric acid Form-DC7, characterized by X-ray powder diffraction pattern, comprising three or more peaks selected from at 5.27, 7.87, 11.43, 12.61, 13.66, 14.69, 15.17, 16.02, 17.39, 18.4, 19.1, 19.71, 20.53, 21.18, 22.71, 23.28, 24.34, 24.91, 25.46, 26.28, 26.73, 27.84, 28.78, 30.23, 30.78, 32.65, 33.35, 34.31, 36.6, 37.4 and 37.84 ± 0.2 degrees 2-theta.

8. The salt or co-crystal of claim 1, wherein the form is Rimegepant Fumaric acid Form-DC2d, characterized by X-ray powder diffraction pattern, comprising three or more peaks selected from at 5.2, 10.69, 11.87, 14.3, 14.68, 15.47, 17.08, 17.47, 18.26, 23.81, 24.82 and 25.8 ± 0.2 degrees 2-theta.

9. The salt or co-crystal of claim 1, wherein the form is Rimegepant Fumaric acid Form-DC2e, characterized by X-ray powder diffraction pattern, comprising three or more peaks selected from at 5.75, 6.49, 9.6, 11.62, 12.06, 12.79, 13.17, 13.81, 14.53, 14.95, 15.51, 16.32, 16.67, 17.42, 18.53, 19.39, 20.76, 20.83, 21.78, 22.94, 23.59, 23.92, 24.3, 24.99, 25.92, 26.64, 27.81, 28.51, 29.01, 29.82, 30.95, 35.41, 37.09 and 39.5 ± 0.2 degrees 2-theta.

10. The salt or co-crystal of claim 1, wherein the form is amorphous Rimegepant Phosphate, characterized by PXRD as depicted in Figure 8.

11. A process for preparation of salts or co-crystals of Rimegepant, comprising:a) suspending or dissolving Rimegepant and a suitable salt forming agent or co-former in a suitable solvent, (OR)suspending or dissolving salts or co-crystals of Rimegepant in a suitable solvent, b) optionally stirring the step a) reaction mass; andc) isolating the salt or co-crystal of Rimegepant.

12. The process of claim 11, wherein the solvent is selected from acetone, methanol, isopropyl alcohol, tetrahydrofuran, methyl tert-butyl ether, dichloromethane, acetonitrile, ethyl acetate, heptane, water, or mixtures thereof.

13. The process of claim 11, wherein the salt or co-crystal is isolated by precipitation, crystallization, filtration, or decantation, followed by drying.

14. A process for preparation of salt or co-crystal of Rimegepant Phosphoric acid Form-DC7, comprising:a) suspending or dissolving Rimegepant in a suitable solvent,b) adding phosphoric acid to the step a) reaction mass (Or) adding the step a) reaction mass to phosphoric acid,c) optionally stirring the step b) reaction mass;d) optionally concentrating the reaction mass and adding a suitable solvent to the reaction mass,e) optionally stirring the step d) reaction mass; andf) isolating the salt or co-crystal of Rimegepant.

15. The process of claim 14, wherein the solvent is selected from dichloromethane, tetrahydrofuran, Isopropyl alcohol, or mixtures thereof.

16. The process of claim 14, wherein the salt or co-crystal is isolated by precipitation, crystallization, filtration, or decantation, followed by drying.

17. A pharmaceutical composition comprising a salt or co-crystal of Rimegepant as claimed in claim 1, and one or more pharmaceutically acceptable excipients or polymers.

18. The pharmaceutical composition of claim 17, wherein the composition is formulated for oral administration.

19. The pharmaceutical composition of claim 17, wherein the composition is used for treatment of migraine with or without aura or preventative treatment of episodic migraine.

20. The salt or co-crystal claimed in claim 2 to 19, wherein the form is stable under thermal, humid, and stress conditions.

21. Use of the salts or co-crystals of Rimegepant claimed in claim 1 to 20 for preparation of other solid-state forms of Rimegepant.

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