WO2024047571A1 - Dérivés de cocristaux de crisaborole - Google Patents

Dérivés de cocristaux de crisaborole Download PDF

Info

Publication number
WO2024047571A1
WO2024047571A1 PCT/IB2023/058612 IB2023058612W WO2024047571A1 WO 2024047571 A1 WO2024047571 A1 WO 2024047571A1 IB 2023058612 W IB2023058612 W IB 2023058612W WO 2024047571 A1 WO2024047571 A1 WO 2024047571A1
Authority
WO
WIPO (PCT)
Prior art keywords
crisaborole
derivative
trq03
approx
analysis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2023/058612
Other languages
English (en)
Inventor
Guilherme SAVOI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO2024047571A1 publication Critical patent/WO2024047571A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
    • C07D213/67—2-Methyl-3-hydroxy-4,5-bis(hydroxy-methyl)pyridine, i.e. pyridoxine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
    • C07D473/12—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1, 3, and 7, e.g. caffeine

Definitions

  • the present invention pertains to the field of pharmaceutical solid forms of Crisaborole, particularly methods of making such solid forms with varying dissolution properties and uses thereof for various medical treatments. More particularly the pharmaceutical forms are Crisaborole cocrystals obtained with caffeine, picolinic acid, quinaldic acid and pyridoxine as coformers.
  • the present invention refers to derivatives of 4-((1 -Hydroxy-1 ,3- dihydrobenzo[c][1 ,2]oxaborol-5-yl)oxy)benzonitrile (Crisaborole).
  • Crisaborole is a nonsteroidal topical medication used for the treatment of mild-to-moderate atopic dermatitis in adults and children. It is a phosphodiesterase 4 (PDE-4) inhibitor. PDE-4 inhibition results in increasing levels of intracellular cyclic adenosine monophosphate.
  • Crisaborole cocrystals only one example was reported in literature, with the species arising from the reaction of Crisaborole with 4,4'- Bipyridine (Cryst. Growth Des. 2018, 18, 4416). No other derivatives were found in literature.
  • Cocrystals are crystalline molecular complexes of two or more nonvolatile compounds bound together in a crystal lattice by non-ionic interactions.
  • Pharmaceutical cocrystals are cocrystals of a therapeutic compound, e.g., an active pharmaceutical ingredient (API), and one or more non-volatile compound(s) (referred to herein as coformer).
  • a coformer in a pharmaceutical cocrystal is typically a non-toxic pharmaceutically acceptable molecule, such as, for example, food additives, preservatives, pharmaceutical excipients, or other APIs.
  • a cocrystal of an API is a distinct chemical composition of the API and coformer(s) and generally possesses distinct crystallographic and spectroscopic properties when compared to those of the API and coformer(s) individually. Crystallographic and spectroscopic properties of crystalline forms are typically measured by X-ray powder diffraction (XRPD) and single crystal X-ray crystallography, among other techniques. Cocrystals often also exhibit distinct thermal behavior. Thermal behavior is measured in the laboratory by such techniques as capillary melting point, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).
  • TGA thermogravimetric analysis
  • DSC differential scanning calorimetry
  • cocrystals may possess more favorable solid state, physical, chemical, pharmaceutical and/or pharmacological properties or may be easier to process than known forms or formulations of the API.
  • a cocrystal may have different dissolution and/or solubility properties than the API, and can, therefore, be more effective in therapeutic delivery.
  • Crisaborole this may include more rapid skin permeation due to enhanced aqueous dissolution to favor formulation or alternatively a controlled slower release formulation due to reduced aqueous dissolution.
  • the skin is a multicomplex membrane and changes from an avascular and lipophilic structure (stratum corneum) to a more aqueous structure (the viable epidermis and dermis).
  • a cocrystal may also affect other pharmaceutical parameters such as storage stability, compressibility and density (useful in formulation and product manufacturing), permeability, and hydrophilic or lipophilic character.
  • New pharmaceutical compositions comprising a cocrystal of a given API, therefore, may have attractive or superior properties as compared to its natural state or existing drug formulations.
  • Figure 1 is the XRPD pattern of solid TRQ03-CAF NP01 isolated from SL experiment using CAF.
  • Figure 2 is the 1 HNMR spectrum of TRQ03-CAF NP01 .
  • Figure 3 is the FT-IR spectrum of TRQ03-CAF NP01 .
  • Figure 4 shows the DSC profile of TRQ03-CAF NP01 .
  • Figure 5 is the TGA profile of TRQ03-CAF NP01 .
  • Figure 6 is the XRPD pattern of solid TRQ03-PIC NP01 isolated from SL experiment using PIC.
  • Figure 7 is the 1 HNMR spectrum of TRQ03-PIC NP01.
  • the structures of Crisaborole and picolinic acid are included to specify some of the signals.
  • Figure 8 is the FT-IR spectrum of TRQ03-PIC NP01 .
  • Figure 9 is the DSC profile of TRQ03-PIC NP01 .
  • Figure 10 is the TGA profile of TRQ03-PIC NP01 .
  • Figure 11 is the XRPD pattern of solid TRQ03-QNL NP01 isolated from SL experiment using QNL.
  • Figure 12 is the 1 HNMR spectrum of TRQ03-QNL NP01. The structures of Crisaborole and quinaldic acid are included to specify some of the signals.
  • Figure 13 is the FT-IR spectrum of TRQ03-QNL NP01 .
  • Figure 14 is the DSC profile of TRQ03-QNL NP01 .
  • Figure 15 is the TGA profile of TRQ03-QNL NP01 .
  • Figure 16 is the XRPD pattern of solid TRQ03-PYX NP01 isolated from SL experiment using PYX.
  • Figure 17 is the 1 HNMR spectrum of TRQ03-PYX NP01. The structures of Crisaborole and pyridoxine are included to specify some of the signals.
  • Figure 18 is the FT-IR spectrum of TRQ03-PYX NP01 .
  • Figure 19 is the TGA profile of TRQ03-PYX NP01 .
  • Figure 20 is the DSC profile of TRQ03-PYX NP01 .
  • Figure 21 is a comparative dissolution profile of TRQ03-CAF NP01 , TRQ03-PIC NP01 , TRQ03-QNL NP01 , TRQ03-PYX NP01 , and Crisaborole as- is.
  • the object of the present invention is to provide new cocrystals of Crisaborole having varied dissolution properties over the pure drug, methods of making such solid forms and uses thereof for various medical treatments.
  • the disease or condition is selected from: psoriasis and allergic dermatitis which are non-infectious inflammatory diseases with chronic and recurrent disease.
  • psoriasis and allergic dermatitis which are non-infectious inflammatory diseases with chronic and recurrent disease.
  • Appropriate treatments can help relieve symptoms and prolong the interval.
  • Cribboron also known as Crisaborole, AN-2728
  • Cribboron is a topical boron-containing anti-inflammatory compound developed by Anacor Pharmaceuticals Inc.
  • Crisaborole has a good therapeutic effect on skin diseases such as psoriasis and allergic dermatitis. It was approved by the US FDA on December 14, 2016.
  • a Crisaborole cocrystal was prepared named TRQ03-CAF NP01 using caffeine as the coformer.
  • a Crisaborole cocrystal was prepared named TRQ03-PIC NP01 using picolinic acid as the coformer.
  • a Crisaborole cocrystal was prepared named TRQ03-QNL NP01 using quinaldic acid as the coformer.
  • a Crisaborole cocrystal was prepared named TRQ03-PYX NP01 using pyridoxine as the coformer. Preparation and evaluation of the preferred cocrystals of the invention
  • Crisaborole (4 g) and 1 .2 equivalents of Caffeine (3.713 g) were weighed in a 100 mL reactor vessel equipped with an anchor stirrer. Ethanol/Water 1 :1 v/v mixture (80 mL) was added, and the reaction mixture was stirred at 300 rpm overnight. The almost complete dissolution of the suspended powders occurred after the solvent addition, followed by the immediate precipitation of a solid.
  • Figure 3 shows the FT-IR spectrum of TRQ03-CAF NP01 and the peaks list can be found in the table below.
  • the DSC profile ( Figure 4) showed a broad endothermic event at 86.5°C (Onset 71 ,6°C).
  • Crisaborole (4 g) and 1.2 equivalents of picolinic acid (2.354 g) were weighed in a 100 mL reactor vessel equipped with an anchor stirrer. Methanol (80 mL) was added, and the reaction mixture was stirred at 300 rpm overnight. The almost complete dissolution of the suspended powders occurred after the solvent addition, followed by the immediate precipitation of a solid.
  • the solid was isolated by vacuum filtration using a buchner filter equipped with a 55 mm por. 42 paper filter, washed with 8 mL of solvent, and dried on the filter for approx. 15 minutes. The recovery of the desired derivative was confirmed by XRPD analysis.
  • Figure 8 shows the FT-IR spectrum of TRQ03-PIC NP01 and the peaks list can be found in the table below.
  • Crisaborole (2.5 g) and 1 .2 equivalents of quinaldic acid (2.069 g) were weighed in a 100 mL reactor vessel equipped with an anchor stirrer. Methanol (50 mL) was added, and the reaction mixture was stirred at 300 rpm overnight. The almost complete dissolution of the suspended powders occurred after the solvent addition, followed by the immediate precipitation of a solid.
  • the solid was isolated by vacuum filtration using a buchner filter equipped with a 55 mm por. 42 paper filter, washed with 8 mL of solvent, and dried on the filter for approx. 15 minutes.
  • Figure 13 shows the FT-IR spectrum of TRQ03-QNL NP01 and the peaks list can be found in the table below.
  • Crisaborole (4 g) and 1.2 equivalents of pyridoxine (3.235 g) were weighed in a 100 mL reactor vessel equipped with an anchor stirrer. Methanol (80 mL) was added, and the reaction mixture was stirred at 300 rpm overnight. The almost complete dissolution of the suspended powders occurred after the solvent addition, followed by the immediate precipitation of a solid.
  • Figure 18 shows the FT-IR spectrum of TRQ03-PYX NP01 and the peaks list can be found in the table below.
  • the DSC profile ( Figure 20) showed a broad endothermic event at 112.7°C (Onset 82.1 °C), followed by a second small endothermic event at 169.6°C (Onset 165.0°C) and an exothermic event at 176.0°C (Onset 171.9°C).
  • the solubility of the prepared Crisaborole derivatives was evaluated through powder dissolution experiments.
  • approx. 225 mg of sample were added to 600 mL of dissolution medium (pH 6.8 potassium phosphate buffer) and the resulting mixture was stirred at 37 °C and 100 rpm. Aliquots were withdrawn from the flask at regular intervals and then injected in HPLC.
  • Table 7 summarizes the results of powder dissolution tests conducted with TRQ03-SM and scale-up cocrystals prepared with CAF, PIC, PYX and QNL.
  • Crisaborole the pure drug showed a dissolution maximum under the investigated conditions after approx. 2 hours of analysis (14.1% of powder dissolved). After this time, a decrease of the concentration of the API was observed (6 hours, 10.5% of powder dissolved), then followed by a slow increase until the final value of 14.6% of powder dissolved.
  • TRQ03CAF NP01 a dissolution maximum was observed after approx. 2 hours of analysis, and a value of 19.0% of powder dissolved. Moreover, after this time, a decrease of the concentration of Crisaborole was observed, with the minimum reached after approx. 6 hours (14.3% of powder dissolved) readily followed by an apparently slight increase of the dissolved powder concentration, until a final value of 19.6% of powder dissolved.
  • TRQ03PIC NP01 the maximum dissolution was reached after approx. 4 hours of analysis (16.1% of powder dissolved), followed by a decrease (6 hours, 12.2% of powder dissolved) and a further increase of the amount of dissolved Crisaborole, until a final value of 17.3% of powder dissolved after 24 hours of analysis.
  • TRQ03PYX NP01 the dissolution profile showed 15.2% of powder dissolved after approx. 2 hours of analysis, then the concentration of Crisaborole dissolved in the medium remained almost stable at 15.0% of powder dissolved until the end of the analysis.
  • TRQ03-QNL NP01 the dissolution profile showed 6.2% of powder dissolved after approx. 2 hours of analysis, 15.3% after 6 hours, and the maximum value was observed at the end of the test (24.9% of powder dissolved). It is worth mentioning that this is the highest value observed within the performed experiments, suggesting that TRQ03-QNL NP01 is the most soluble species in the used medium after 24 hours.
  • the caffeine derivative showed a faster dissolution rate with respect to Crisaborole as-is, even at the same order of concentration (only approx. 1.3-fold higher).
  • the picolinic acid derivative showed a slower dissolution rate with respect to Crisaborole as-is (within 2 hours of analysis).
  • the pyridoxine derivative showed the same dissolution kinetics as compared to Crisaborole as-is, but showed a constant profile after 2 hours of analysis.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouveaux dérivés co-cristallins (co-formeurs : caféine, acide picolinique, acide quinaldique et pyridoxine) de 4-((1-hydroxy-1,3- dihydrobenzo[c][1,2]oxaborol-5-yl)oxy)benzonitrile (Crisaborole) ayant une dissolution variée par rapport au crisaborole libre.
PCT/IB2023/058612 2022-09-01 2023-08-31 Dérivés de cocristaux de crisaborole Ceased WO2024047571A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263403025P 2022-09-01 2022-09-01
US63/403,025 2022-09-01

Publications (1)

Publication Number Publication Date
WO2024047571A1 true WO2024047571A1 (fr) 2024-03-07

Family

ID=90099010

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2023/058612 Ceased WO2024047571A1 (fr) 2022-09-01 2023-08-31 Dérivés de cocristaux de crisaborole

Country Status (2)

Country Link
AR (1) AR130361A1 (fr)
WO (1) WO2024047571A1 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017193914A1 (fr) * 2016-05-09 2017-11-16 苏州科睿思制药有限公司 Formes cristallines de crisaborole sous forme libre et procédé de préparation et utilisation de celles-ci
WO2017203514A1 (fr) * 2016-05-26 2017-11-30 Perrigo Api Ltd Polymorphes de crisaborole et procédés pour les produire
WO2018013655A1 (fr) * 2016-07-12 2018-01-18 Pliva Hrvatska D.O.O. Formes à l'état solide de crisaborole
WO2018216032A1 (fr) * 2017-05-23 2018-11-29 Msn Laboratories Private Limited, R&D Center Procédé de préparation de 5-(4-cyanophénoxy)-1,3-dihydro-1-hydroxy- [2,1]-benzoxaborole et ses polymorphes
WO2019120637A1 (fr) * 2017-12-21 2019-06-27 Olon S.P.A. Procédé de préparation de crisaborole
IT201800002347A1 (it) * 2018-02-02 2019-08-02 Dipharma Francis Srl Intermedi e procedimento per la preparazione di una forma cristallina di un farmaco antiinfiammatorio topico
EP3521293A1 (fr) * 2018-02-02 2019-08-07 Dipharma Francis S.r.l. Procédé de préparation d'un inhibiteur de la phosphodiestérase 4
US20210002307A1 (en) * 2016-05-09 2021-01-07 Anacor Pharmaceuticals, Inc. Crystal Forms of Crisaborole In Free Form And Preparation Method And Use Thereof
CN112375093A (zh) * 2020-11-13 2021-02-19 江苏知原药业股份有限公司 一种克立硼罗晶型化合物及其制备方法
CN113087733A (zh) * 2021-04-06 2021-07-09 南京科默生物医药有限公司 克立硼罗的晶型a、晶型b、晶型c、晶型d、晶型e及其制备方法

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017193914A1 (fr) * 2016-05-09 2017-11-16 苏州科睿思制药有限公司 Formes cristallines de crisaborole sous forme libre et procédé de préparation et utilisation de celles-ci
US20210002307A1 (en) * 2016-05-09 2021-01-07 Anacor Pharmaceuticals, Inc. Crystal Forms of Crisaborole In Free Form And Preparation Method And Use Thereof
WO2017203514A1 (fr) * 2016-05-26 2017-11-30 Perrigo Api Ltd Polymorphes de crisaborole et procédés pour les produire
WO2018013655A1 (fr) * 2016-07-12 2018-01-18 Pliva Hrvatska D.O.O. Formes à l'état solide de crisaborole
WO2018216032A1 (fr) * 2017-05-23 2018-11-29 Msn Laboratories Private Limited, R&D Center Procédé de préparation de 5-(4-cyanophénoxy)-1,3-dihydro-1-hydroxy- [2,1]-benzoxaborole et ses polymorphes
WO2019120637A1 (fr) * 2017-12-21 2019-06-27 Olon S.P.A. Procédé de préparation de crisaborole
IT201800002347A1 (it) * 2018-02-02 2019-08-02 Dipharma Francis Srl Intermedi e procedimento per la preparazione di una forma cristallina di un farmaco antiinfiammatorio topico
EP3521293A1 (fr) * 2018-02-02 2019-08-07 Dipharma Francis S.r.l. Procédé de préparation d'un inhibiteur de la phosphodiestérase 4
CN112375093A (zh) * 2020-11-13 2021-02-19 江苏知原药业股份有限公司 一种克立硼罗晶型化合物及其制备方法
CN113087733A (zh) * 2021-04-06 2021-07-09 南京科默生物医药有限公司 克立硼罗的晶型a、晶型b、晶型c、晶型d、晶型e及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CAMPILLO-ALVARADO GONZALO, DIDDEN TIGHE D.; OBURN SHALISA M.; SWENSON DALE C.; MACGILLIVRAY LEONARD R.: "Exploration of Solid Forms of Crisaborole: Crystal Engineering Identifies Polymorphism in Commercial Sources and Facilitates Cocrystal Formation", CRYSTAL GROWTH & DESIGN, vol. 18, no. 8, 1 August 2018 (2018-08-01), US , pages 4416 - 4419, XP093174419, ISSN: 1528-7483, DOI: 10.1021/acs.cgd.8b00375 *

Also Published As

Publication number Publication date
AR130361A1 (es) 2024-11-27

Similar Documents

Publication Publication Date Title
EP3275871B1 (fr) Cristaux
JP2017505347A (ja) ２−ヒドロキシ−６−（（２−（１−イソプロピル−１ｈ−ピラゾール−５−イル）ピリジン−３−イル）メトキシ）ベンズアルデヒドの遊離塩基の結晶多形
JPH0231078B2 (fr)
EP2603503A1 (fr) Mésylate de dabigatran étexilate, ses formes solides et leurs procédés de préparation
WO2021044437A1 (fr) Co-cristaux d'olaparib et leur procédé de préparation
WO2013124385A2 (fr) Formes solides d'étéxilate-mésylate de dabigatran et procédés pour leur préparation
EP2455368B1 (fr) Benzène-sulfonate de 2-[[[2-[(hydroxyacétyl)amino]-4-pyridinyl]méthyl]thio]-n-[4-(trifluorométhoxy)phényl]-3-pyridinecarboxamide, cristaux de celui-ci, ses polymorphes et ses procédés de fabrication
Li et al. Improving the solubility and bioavailability of anti-hepatitis B drug PEC via PEC–fumaric acid cocrystal
RU2385325C2 (ru) Способ получения сульфата атазанавира
WO2024047571A1 (fr) Dérivés de cocristaux de crisaborole
US20240425463A1 (en) Process for manufacturing a diphenylphrazine derivative
TW200900392A (en) Novel crystalline bepotastine metal salt hydrate, method for preparing same, and pharmaceutical composition comprising same
CA3221067A1 (fr) Sel de potassium cristallin de 1-ethyl-n-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)piperidine-4-sulfonamide
EP4301749A1 (fr) Formes solides d'un inhibiteur de cyp11a1 à structure 4h-pyran-4-one
WO2018078383A1 (fr) Composition pharmaceutique comprenant du selexipag amorphe
US20040038985A1 (en) Crystal forms of 1- [6-chloro-5-(trifluoromethly) -2-pyridinyl] piperazine hydrochloride
EP4588915A1 (fr) Forme polymorphe de sel d'addition d'acide nepicastat, son procédé de préparation et son utilisation
EP3898596A1 (fr) Composé pharmaceutique, son procédé de fabrication et son utilisation en tant qu'agent thérapeutique
BR122025018455A2 (pt) Formas sólidas de um composto inibidor de cyp11a1 estruturado com 4h-piran-4-ona, métodos para preparar as mesmas, forma de dosagem farmacêutica e uso das referidas formas sólidas para o tratamento de cânceres hormonalmente regulados
WO2021161347A1 (fr) Nouveaux sels de nilotinib et formes polymorphes de celui-ci
KR20160146428A (ko) 솔리페나신 또는 그의 약학적으로 허용되는 염과 락토즈를 포함하는 안정한 무정형 솔리페나신 약학 조성물 및 그의 제조방법
TW202602855A (zh) ４－［３－（環丙基甲氧基）－４－（二氟甲氧基）苯乙基吡啶－２（１ｈ）－酮的固體形式及其製備方法
WO2022224269A1 (fr) Co-cristaux, sels et formes solides de niraparib
EA051073B1 (ru) Твердые формы 4h-пиран-4-она в качестве структурированного ингибитора cyp11a1
EA043016B1 (ru) Фармацевтическое соединение, способ его получения и применения в качестве лекарственного средства

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23859601

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 23859601

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 23859601

Country of ref document: EP

Kind code of ref document: A1