WO2023181075A1 - Dispersions solides amorphes de deucravacitinib et leurs procédés de préparation - Google Patents

Dispersions solides amorphes de deucravacitinib et leurs procédés de préparation Download PDF

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WO2023181075A1
WO2023181075A1 PCT/IN2023/050280 IN2023050280W WO2023181075A1 WO 2023181075 A1 WO2023181075 A1 WO 2023181075A1 IN 2023050280 W IN2023050280 W IN 2023050280W WO 2023181075 A1 WO2023181075 A1 WO 2023181075A1
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deucravacitinib
poly
amorphous solid
solid dispersion
solvent
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PCT/IN2023/050280
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English (en)
Inventor
Deepika PATHIVADA
Ashok Arige
Saikat Sen
Srinivas ORUGANTI
Rajeev Rehani BUDHDEV
Mohan Kumar KOTTUR
Magesh SAMPATH
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Dr. Reddy's Laboratories Limited
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Publication of WO2023181075A1 publication Critical patent/WO2023181075A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • aspects of the present application relate to amorphous solid dispersions of Deucravacitinib and process for the preparation crystalline form of Deucravacitinib.
  • Deucravacitinib is the first and only new type of oral selective TYK2 inhibitor, clinically used to treat autoimmune and autoinflammatory diseases (such as psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease, Crowe Grace, etc.). Deucravacitinib has been approved by USFDA for the treatment of moderate to severe plaque psoriasis. In addition, Deucravacitinib also shows good therapeutic effects in the treatment of systemic lupus erythematosus and Crohn's disease.
  • autoimmune and autoinflammatory diseases such as psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease, Crowe Grace, etc.
  • Deucravacitinib has been approved by USFDA for the treatment of moderate to severe plaque psoriasis.
  • Deucravacitinib also shows good therapeutic effects in the treatment of systemic lupus erythematosus and Crohn's
  • Deucravacitinib 6-(cyclopropanecarboxamido)-4-[2- methoxy-3-(l-methyl-lH-l,2,4-triazol-3-yl)anilino]-N-(2H3)methylpyridazine-3-carbox amide, the structural formula is shown below.
  • WO2018183656A1 discloses Deucravacitinib crystal form A and its process for the preparation.
  • WO2021129467A1 discloses two crystalline forms of Deucravacitinib (CSI and CSII) and process for the preparation of crystalline Form of CSI.
  • CSI and CSII two crystalline forms of Deucravacitinib
  • CSIII crystalline Form of Deucravacitinib
  • WO2021055652A1 discloses Deucravacitinib dosage form comprising amorphous Deucravacitinib dispersed in a polymer matrix.
  • the present application provides a stable amorphous solid dispersion of Deucravacitinib comprising an amorphous Deucravacitinib and polymer matrix.
  • the present application provides a process for the preparation of stable amorphous solid dispersion of Deucravacitinib and polymer matrix, comprising
  • step (b) optionally heating the reaction mixture obtained in step (a);
  • the present application provides a process for the preparation of stable amorphous solid dispersion of Deucravacitinib and polymer matrix, comprising contacting Deucravacitinib with polymer matrix by grinding in ball mill or by subjecting to hot melt extrusion.
  • the present application provides an amorphous solid dispersion of Deucravacitinib comprising an amorphous Deucravacitinib and cyclodextrin.
  • the present application provides a process for the preparation of amorphous solid dispersion of Deucravacitinib and cyclodextrin, comprising contacting Deucravacitinib with cyclodextrin by grinding in ball mill or by subjecting to hot melt extrusion.
  • the present application provides stable premix of amorphous solid dispersion of Deucravacitinib together with at least one pharmaceutically acceptable polymer matrix and Syloid.
  • the present application provides process for the preparation of stable premix of amorphous solid dispersion of Deucravacitinib together with at least one pharmaceutically acceptable polymer matrix and Syloid, comprising the steps of
  • the present application provides a process for the preparation of crystalline Deucravacitinib, comprising
  • step (c) adding a second solvent for the solution or suspension obtained in step(a) or step (b);
  • Figure 1 is an illustrative X-ray powder diffraction pattern of amorphous solid dispersion of Deucravacitinib and cyclodextrin prepared by the method of Example No 1.
  • Figure 2 is an illustrative X-ray powder diffraction pattern of amorphous solid dispersion of Deucravacitinib and eudragit prepared by the method of Example No 2.
  • Figure 3 is an illustrative X-ray powder diffraction pattern of crystalline form of Deucravacitinib prepared by the method of Example No 3.
  • Figure 4 is an illustrative powder X-ray diffraction pattern of amorphous solid dispersion of Deucravacitinib and Chitosan prepared by the method of Example No 5.
  • Figure 5 is an illustrative powder X-ray diffraction pattern of amorphous solid dispersion of Deucravacitinib and Polyvinyl alcohol prepared by the method of Example No 6.
  • Figure 6 is an illustrative powder X-ray diffraction pattern of amorphous solid dispersion of Deucravacitinib and Alginic acid prepared by the method of Example No 7.
  • Figure 7 is an illustrative powder X-ray diffraction pattern of amorphous solid dispersion of Deucravacitinib and soluplus prepared by the method of Example No 8.
  • Figure 8 is an illustrative powder X-ray diffraction pattern of amorphous solid dispersion of Deucravacitinib and polyvinylpyrrolidone (PVP) K30 prepared by the method of Example No 9.
  • PVP polyvinylpyrrolidone
  • Figure 9 is an illustrative powder X-ray diffraction pattern of amorphous solid dispersion of Deucravacitinib and copovidone prepared by the method of Example No 12.
  • Figure 10 is an illustrative powder X-ray diffraction pattern of a premix of Syloid and amorphous solid dispersion of Deucravacitinb with HPMC prepared by the method of Example No 13.
  • Figure 11 is an illustrative powder X-ray diffraction pattern of amorphous Deucravacitinib with few crystalline peaks prepared by the method of Example No 14.
  • Figure 12 is an illustrative powder X-ray diffraction pattern of stable premix of amorphous Deucravacitinib and syloid prepared by the method of Example No 15.
  • Figure 13 is powder X-ray diffraction pattern illustrating the stability of the premix of amorphous Deucravacitinib with syloid after 12 days of storage in open container at ambient temperature conditions.
  • the present application provides a stable amorphous solid dispersion of Deucravacitinib comprising an amorphous Deucravacitinib and polymer matrix, wherin polymer matrix is selected from cyclodextrin, alginic acid, poly(N- hydroxyethyl acrylamide) (PHEAM), hydroxyethyl methacrylate, poly(vinyl alcohol), poly(acrylic acid), polyvinyl acetate, polyvinylchloride, polyethylene imine), poly(N-isopropyl acrylamide), poly(4-vinylphenol), polypropylene, poly(sodium 4-styrenesulfonate), polyethyleneglycol 6000, polyethyl ene-polypropylene glycol 188, poly(ethylene oxide), poly(chloromethylstyrene-co-styrene), alginate, poly(ethylene glycol)-block-poly(lactic acid), poly(ethylene oxide)-poly
  • the present application provides a process for the preparation of stable amorphous solid dispersion of Deucravacitinib and polymer matrix, comprising
  • step (a) providing a solution or suspension of Deucravacitinib and polymer matrix in a solvent; (b) optionally heating the reaction mixture obtained in step (a); and
  • Step (a) involves the providing a solution or suspension of Deucravacitinib and polymer matrix in a solvent
  • Providing a solution or suspension of Deucravacitinib includes: i) direct use of a reaction mixture containing Deucravacitinib that is obtained in the course of its synthesis; or ii) dissolving or suspending Deucravacitinib in a solvent
  • Deucravacitinib Any physical form of Deucravacitinib including solvates, hydrates, anhydrous or amorphous may be utilized for providing solution or suspension of Deucravacitinib.
  • Suitable polymer matrix that may be used in step (a) is selected from cyclodextrin, alginic acid, poly(N-hydroxyethyl acrylamide) (PHEAM), hydroxyethyl methacrylate, poly(vinyl alcohol), poly(acrylic acid), polyvinyl acetate, polyvinylchloride, poly (ethylene imine), poly(N-isopropyl acrylamide), poly (4- vinylphenol), polypropylene, poly(sodium 4-styrenesulfonate), polyethyleneglycol 6000, polyethyl ene-polypropylene glycol 188, poly(ethylene oxide), poly(chloromethylstyrene-co-styrene), alginate, polyethylene glycol)-block-poly(lactic acid), poly(ethylene oxide)-poly(propylene oxide) triblock, chitosan, polyvinyl alcohol, soluplus, syloid, eudragit, polyvinylpyrrol
  • Suitable solvents that may be used in step (a) is selected from methanol, ethanol, 2-propanol, 1 -butanol, 2-butanol, 1 -pentanol, 2-pentanol, 3 -pentanol, di chloromethane, tetrahydrofuran, 1,4-di oxane, acetone, methyl ethyl ketone, methyl isobutyl ketone; methyl acetate, ethyl acetate, isopropyl acetate, water or mixtures thereof.
  • Deucravacitinib can be dissolved or suspended in a solvent or mixture of one or more solvents.
  • the dissolution or suspension temperatures may range from about 0°C to about the reflux temperature of the solvent, or less than about 100°C, less than about 70°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 10°C, or any other suitable temperatures without affecting its quality.
  • a solution of Deucravacitinib and polymer matrix may be filtered to make it clear and free of unwanted particles.
  • the obtained solution may be optionally treated with an adsorbent material, such as carbon and/or hydrose, to remove colored components, etc., before filtration.
  • Step (c) involves isolating amorphous solid dispersion of Deucravacitinib.
  • Isolating amorphous solid dispersion of Deucravacitinib in step (c) may involve removal of solvent by employing techniques like solvent evaporation under atmospheric pressure or reduced pressure / vacuum such as a rotational distillation using Biichi® Rotavapor®, spray drying, freeze drying, thin film drying, agitated thin film drying, rotary vacuum paddle dryer (RVPD) and the like.
  • solvent evaporation under atmospheric pressure or reduced pressure / vacuum
  • RVPD rotary vacuum paddle dryer
  • the recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, agitated nutsche filter & dryer or the like.
  • the drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the Deucravacitinib is not degraded in quality.
  • the drying may be carried out for any desired times until the required product quality is achieved.
  • the dried product may optionally be subjected to a size reduction procedure to produce desired particle sizes. Milling or micronization may be performed before drying, or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer milling, and jet milling.
  • the present application provides a process for the preparation of stable amorphous solid dispersion of Deucravacitinib and polymer matrix, comprising contacting Deucravacitinib with polymer matrix by grinding in ball mill or by subjecting to hot melt extrusion.
  • the present application provides an amorphous solid dispersion of Deucravacitinib comprising an amorphous Deucravacitinib and cyclodextrin.
  • the present application provides a process for the preparation of amorphous solid dispersion of Deucravacitinib and cyclodextrin, comprising contacting Deucravacitinib with cyclodextrin by grinding in ball mill or by subjecting to hot melt extrusion.
  • the present application provides stable premix of amorphous solid dispersion of Deucravacitinib together with at least one pharmaceutically acceptable polymer matrix and Syloid.
  • the present application provides process for the preparation of stable premix of amorphous solid dispersion of Deucravacitinib together with at least one pharmaceutically acceptable polymer matrix and Syloid, comprising the steps of
  • Step (a) involves the providing a solution or suspension of Deucravacitinib and polymer matrix in a solvent
  • Providing a solution or suspension of Deucravacitinib includes: i) direct use of a reaction mixture containing Deucravacitinib that is obtained in the course of its synthesis; or ii) dissolving or suspending Deucravacitinib in a solvent
  • Deucravacitinib Any physical form of Deucravacitinib including solvates, hydrates, anhydrous or amorphous may be utilized for providing solution or suspension of Deucravacitinib.
  • Suitable solvents that may be used in step (a) is selected from methanol, ethanol, 2-propanol, 1 -butanol, 2-butanol, 1 -pentanol, 2-pentanol, 3 -pentanol, di chloromethane, tetrahydrofuran, 1,4-di oxane, acetone, methyl ethyl ketone, methyl isobutyl ketone; methyl acetate, ethyl acetate, isopropyl acetate, water or mixtures thereof.
  • Step (b) involves isolating amorphous solid dispersion of Deucravacitinib.
  • Isolating amorphous solid dispersion of Deucravacitinib in step (c) may involve removal of solvent by employing techniques like solvent evaporation under atmospheric pressure or reduced pressure / vacuum such as a rotational distillation using Biichi® Rotavapor®, spray drying, freeze drying, thin film drying, agitated thin film drying, rotary vacuum paddle dryer (RVPD) and the like.
  • solvent evaporation under atmospheric pressure or reduced pressure / vacuum
  • RVPD rotary vacuum paddle dryer
  • the present application provides a process for the preparation of crystalline Deucravacitinib, comprising
  • step (c) adding a second solvent for the solution or suspension obtained in step(a) or step (b);
  • Suitable solvents that may be used in step (a) is selected from methanol, di chloromethane, dimethyl sulfoxide (DMSO), ethanol, 2-propanol, 1 -butanol, 2- butanol, 1 -pentanol, 2-pentanol, 3 -pentanol, tetrahydrofuran, 1,4-di oxane, acetone, methyl ethyl ketone, methyl isobutyl ketone; methyl acetate, ethyl acetate, isopropyl acetate or mixtures thereof.
  • DMSO dimethyl sulfoxide
  • Suitable second solvent that may be used in step (c) is selected from water, hexane, heptane, cyclohexane, dioxane or mixtures thereof.
  • the solution of Deucravacitinib may be contacted with second solvent is added rapidly in single lot or gradually in multiple lots.
  • Isolation of crystalline form of Deucravacitinib may involve methods including cooling, concentrating the mass, adding seed crystals to induce crystallization, or the like. Stirring or other alternate methods such as shaking, agitation, or the like, may also be employed for the isolation.
  • the crystalline forms of Deucravacitinib may be recovered by methods including decantation, centrifugation, gravity filtration, suction filtration, agitated nutsche filter & dryer or any other technique for the recovery of solids under pressure or under reduced pressure.
  • the recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, agitated nutsche filter & dryer or the like.
  • the drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the Deucravacitinib is not degraded in quality.
  • the drying may be carried out for any desired times until the required product quality is achieved.
  • amorphous solid dispersion of Deucravacitinib is analyzed in different temperature at different humidity conditions and the results indicates that the amorphous form remained stable after 3 months in all the conditions. Stability studies details are provided in the below table.
  • amorphous solid dispersion of Deucravacitinib and polymer, comprising the ratio of Deucravacitinib and polymer is 1 : 1 to 1 :5 w/w.
  • Figure 13 is a powder X-ray diffraction pattern illustrating the stability of the premix of amorphous Deucravacitinib with Syloid after 12 days of storage in open container at ambient temperature conditions.
  • Example-1 Process for the preparation of amorphous solid dispersion of Deucravacitinib and cyclodextrin.
  • Deucravacitinib (lOOmg) and Beta cyclodextrin (lOOmg) were taken into ball milling capsule and milled for 90 minutes.
  • Example-2 Process for the preparation of amorphous solid dispersion of Deucravacitinib and eudragit.
  • Deucravacitinib 500 mg
  • Eudragit L100 55 500 mg
  • the obtained clear solution was evaporated under reduced pressure at 65°C to obtain amorphous solid dispersion of Deucravacitinib and eudragit.
  • Example-3 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib (200 mg) was dissolved in methanol (90 mL) at 65°C. Water (50 mL) was added to the solution at 31 °C and stirred the mixture at the same temperature for 6 hours. The obtained solid was filtered and dried under vacuum to get the title compound.
  • Example-4 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib 500 mg was dissolved in dichloromethane (30 mL) at 40°C and the solution was filtered to make it particle free.
  • Example-5 Process for the preparation of amorphous solid dispersion of Deucravacitinib and Chitosan.
  • Deucravacitinib 250mg
  • Beta Chitosan 750mg
  • Example-6 Process for the preparation of amorphous solid dispersion of Deucravacitinib and Polyvinyl alcohol.
  • Deucravacitinib (2.5 g) dissolved in methanol (500 mL), Polyvinyl alcohol (2.5 g) dissolved in water (100 mL) at 70°C. Blended both the solutions and filtered to make it particle free. The obtained clear solution was spray dried to obtain amorphous solid dispersion of Deucravacitinib and Polyvinyl alcohol.
  • Example-7 Process for the preparation of amorphous solid dispersion of Deucravacitinib and Alginic acid.
  • Deucravacitinib 250mg
  • Alginic acid 750mg
  • Example-8 Process for the preparation of amorphous solid dispersion of Deucravacitinib and Soluplus.
  • Deucravacitinib 500 mg
  • Soluplus 1.5 g
  • methanol 150 mL
  • the obtained clear solution was evaporated under reduced pressure at 70 °C to obtain amorphous solid dispersion of Deucravacitinib and Soluplus.
  • Example-9 Process for the preparation of amorphous solid dispersion of Deucravacitinib and polyvinylpyrrolidone (PVP) K30.
  • Deucravacitinib 50 mg
  • PVP polyvinylpyrrolidone
  • Example-10 Process for the preparation of amorphous solid dispersion of Deucravacitinib and polyvinylpyrrolidone (PVP) K30.
  • Deucravacitinib 100 mg
  • polyvinylpyrrolidone (PVP) K30 200 mg
  • the solution was filtered to make it particle free.
  • the obtained clear solution was concentrated under reduced pressure at 45 °C to obtain the title compound.
  • Example-11 Process for the preparation of amorphous solid dispersion of Deucravacitinib and polyvinylpyrrolidone (PVP) K30.
  • Deucravacitinib 150 mg
  • PVP polyvinylpyrrolidone
  • Example-12 Process for the preparation of amorphous solid dispersion of Deucravacitinib and copovidone.
  • Example-13 Process for the preparation of premix of amorphous solid dispersion of Deucravacitinib with HPMC and Syloid.
  • Deucravacitinib 150 mg
  • HPMC 150 mg
  • the solution was filtered to make it particle free.
  • the obtained clear solution was concentrated under reduced pressure at 45 °C to obtain solid dispersion of Deucravacitinib and HPMC as a sticky solid.
  • Syloid 244 FP 150 mg was added to the sticky solid and the mixture obtained was ground for 1 hour to obtain the title compound.
  • Example-14 Process for the preparation of amorphous Deucravacitinib with few crystalline peaks.
  • Deucravacitinib (250 mg) was dissolved in 10% methanol in dichloromethane (15 mL). The solution was filtered to make it particle free. The obtained clear solution was concentrated rapidly under reduced pressure at 45 °C to obtain the title compound.
  • Example-15 Process for the preparation of stable premix of amorphous Deucravacitinib and Syloid.
  • Deucravacitinib 150 mg was dissolved in 10% methanol in dichloromethane (20 mL). The solution was filtered to make it particle free.
  • Syloid 244 FP 150 mg was added to the clear solution. The obtained mixture was concentrated rapidly to dryness under reduced pressure at 45 °C to obtain the title compound.
  • Example-16 Process for the preparation of stable premix of amorphous Deucravacitinib and Syloid.
  • Deucravacitinib 200 mg was dissolved in a mixture of 1,4-di oxane (10 mL) and water (15 mL) at 50 °C. The solution was filtered to make it particle free. The obtained solution was frozen and then lyophilized for 18 hours to obtain dry material. Syloid (150 mg) was added to the obtained dry material and the mixture was ground for 15 minutes to obtain the title compound.
  • Example-17 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib (200 mg) was dissolved in dimethyl sulfoxide (5 mL) at 50 °C. The obtained solution was slowly added to water (100 mL) at 0 °C. The resultant mixture was stirred at 25 °C for 3 hours. The obtained solid was filtered and dried under vacuum to obtain the title compound.
  • Example-18 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib (300 mg) was dissolved in 10% methanol in dichloromethane (15 mL). The solution was filtered to make it particle free. n-Hexane (45 mL) was added to the solution at 27 °C and the resultant mixture was stirred at the same temperature for 3 hours. The obtained solid was filtered and dried under vacuum to obtain the title compound.
  • Example-19 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib (300 mg) was dissolved in N-Methyl-2 -Pyrrolidone (2 mL) at 70 °C. n- butanol (5 mL) was added to the solution at 27 °C and the resultant mixture was stirred at the same temperature for 2 hours. The obtained suspension was cooled to 0 °C and stirred at the same temperature for 15-20 min. The resultant suspension was filtered and dried under vacuum to obtain the title compound.
  • Example-20 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib 250 mg was dissolved in N-Methyl-2 -Pyrrolidone (2 mL) at 65 °C.
  • Methanol (4 mL) was added to the solution at 27 °C and the resultant mixture was stirred at the same temperature for 2 hours.
  • the obtained suspension was cooled to 0 °C and stirred at the same temperature for 15-20 min.
  • the resultant suspension was filtered and dried under vacuum to obtain the title compound.
  • Example-21 Process for the preparation of crystalline form of Deucravacitinib.
  • Deucravacitinib 250 mg was dissolved in 10% methanol in di chloromethane (15 mL). The solution was filtered to make it particle free and then concentrated to dryness under reduced pressure at 40 °C. Ethyl acetate (500 mL) was added to the residue obtained and the mixture was stirred at 27 °C for 2 hours. The solution obtained was filtered to make it particle free and then concentrated under reduced pressure at 40 °C to obtain the title compound.

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Abstract

La présente invention concerne des dispersions solides amorphes de deucravacitinib, un procédé pour la préparation d'une dispersion solide amorphe de deucravacitinib, un procédé de préparation de la forme cristalline de deucravacitinib et un procédé pour la préparation d'un prémélange stable de dispersion solide amorphe de deucravacitinib conjointement avec au moins une matrice polymère pharmaceutiquement acceptable et un syloïde.
PCT/IN2023/050280 2022-03-24 2023-03-23 Dispersions solides amorphes de deucravacitinib et leurs procédés de préparation WO2023181075A1 (fr)

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IN202241016761 2022-03-24
IN202241016761 2022-03-24
IN202241030322 2022-05-26
IN202241030322 2022-05-26
IN202241042926 2022-07-27
IN202241042926 2022-07-27

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024176263A1 (fr) * 2023-02-22 2024-08-29 Cipla Limited Dispersions solides amorphes de deucravacitinib et leurs polymorphes

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018183656A1 (fr) * 2017-03-30 2018-10-04 Bristol-Myers Squibb Company Forme cristalline du 6-(cyclopropanecarboxamido)-4-((2-méthoxy-3-(1-méthyl-1h-1,2,4-triazol-3-yl)phényl)amino)-n-(méthyl-d3)pyridazine-3-carboxamide
WO2021055652A1 (fr) * 2019-09-18 2021-03-25 Bristol-Myers Squibb Company Formes posologiques d'inhibiteurs de tyk2
WO2021129467A1 (fr) * 2019-12-27 2021-07-01 苏州科睿思制药有限公司 Forme cristalline bms-986165, son procédé de préparation et son utilisation
WO2022083649A1 (fr) * 2020-10-20 2022-04-28 杭州领业医药科技有限公司 Forme cristalline d'un dérivé pyridazinique

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018183656A1 (fr) * 2017-03-30 2018-10-04 Bristol-Myers Squibb Company Forme cristalline du 6-(cyclopropanecarboxamido)-4-((2-méthoxy-3-(1-méthyl-1h-1,2,4-triazol-3-yl)phényl)amino)-n-(méthyl-d3)pyridazine-3-carboxamide
WO2021055652A1 (fr) * 2019-09-18 2021-03-25 Bristol-Myers Squibb Company Formes posologiques d'inhibiteurs de tyk2
WO2021129467A1 (fr) * 2019-12-27 2021-07-01 苏州科睿思制药有限公司 Forme cristalline bms-986165, son procédé de préparation et son utilisation
WO2022083649A1 (fr) * 2020-10-20 2022-04-28 杭州领业医药科技有限公司 Forme cristalline d'un dérivé pyridazinique

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024176263A1 (fr) * 2023-02-22 2024-08-29 Cipla Limited Dispersions solides amorphes de deucravacitinib et leurs polymorphes

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