Febuxostat–p-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature

The multi-component solid form of febuxostat (FEB) with p-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), and infrared spectros...

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Veröffentlicht in:Crystals (Basel) Jg. 13; H. 5; S. 836
Hauptverfasser: Ungur, Doriana T., Santiso-Quinones, Gustavo, Pop, Mihaela M., Tamas, Tudor L., Guguta, Carmen, Stam, Danny, Mija, Alice, Iordache, Coca A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basel MDPI AG 18.05.2023
Schlagworte:
Aging
Basicity
Bioavailability
Cooling
Crystal growth
Crystal structure
Crystallization
Crystals
Dissolution
Evaporative cooling
febuxostat
Fourier transforms
FT-IR
High temperature
Infrared spectroscopy
p-toluenesulfonic acid
Pharmaceutical industry
Pharmacokinetics
Relative humidity
Rheumatism
salt/co-crystal
SC-XRD
Solvents
Thermogravimetry
Uric acid
X ray powder diffraction
ISSN:2073-4352, 2073-4352
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Abstract The multi-component solid form of febuxostat (FEB) with p-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), and infrared spectroscopy (FT-IR). The multi-component form was stable after exposure at elevated temperature and relative humidity and powder dissolution measurements revealed five-fold aqueous solubility improvement relative to FEB. Additionally, the decrease in pH after dissolution suggests a potential for enhancing the drug absorption in the lower stomach. In the context of the regulatory requirements, the salt/co-crystal nature of the form was elucidated by a combination of crystallization process development and crystal growth, followed by SC-XRD and FT-IR. Despite the very weak basicity of the drug, crystal structure determination combined with spectroscopy analysis revealed salt formation by the transfer of the acidic proton from p-toluenesulfonic acid to FEB. Our study emphasizes the importance of the crystal structure knowledge in understanding the type of interactions present in multi-component crystals as well as complying with the specific regulatory requirements.
AbstractList The multi-component solid form of febuxostat (FEB) with p-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), and infrared spectroscopy (FT-IR). The multi-component form was stable after exposure at elevated temperature and relative humidity and powder dissolution measurements revealed five-fold aqueous solubility improvement relative to FEB. Additionally, the decrease in pH after dissolution suggests a potential for enhancing the drug absorption in the lower stomach. In the context of the regulatory requirements, the salt/co-crystal nature of the form was elucidated by a combination of crystallization process development and crystal growth, followed by SC-XRD and FT-IR. Despite the very weak basicity of the drug, crystal structure determination combined with spectroscopy analysis revealed salt formation by the transfer of the acidic proton from p-toluenesulfonic acid to FEB. Our study emphasizes the importance of the crystal structure knowledge in understanding the type of interactions present in multi-component crystals as well as complying with the specific regulatory requirements.
Author Santiso-Quinones, Gustavo
Ungur, Doriana T.
Pop, Mihaela M.
Guguta, Carmen
Mija, Alice
Tamas, Tudor L.
Iordache, Coca A.
Stam, Danny
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  fullname: Ungur, Doriana T.
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  surname: Santiso-Quinones
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  givenname: Mihaela M.
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  givenname: Tudor L.
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  surname: Iordache
  fullname: Iordache, Coca A.
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CitedBy_id crossref_primary_10_1016_j_molstruc_2023_136596
crossref_primary_10_3390_molecules29235631
crossref_primary_10_1016_j_jelechem_2025_119281
crossref_primary_10_1016_j_molstruc_2025_143294
Cites_doi 10.1186/s13075-018-1633-9
10.2174/138527211798357074
10.1111/j.1365-2125.2007.03016.x
10.1107/S2053229614024218
10.1038/nrd2831
10.1016/j.molstruc.2018.08.098
10.1016/j.molstruc.2016.10.044
10.1021/mp0601345
10.1021/cg400638g
10.3390/cryst8020085
10.1080/02652048.2018.1526339
10.1016/S0140-6736(10)60665-4
10.3390/cryst7120365
10.15171/jrip.2017.57
10.1016/S0889-857X(21)00887-5
10.1016/j.berh.2010.10.004
10.1155/2021/3834368
10.1021/cg400583z
10.1016/j.molstruc.2017.02.052
10.1016/j.ajps.2016.05.009
10.1038/s41598-019-53965-x
10.1186/s41120-016-0003-4
10.1038/s41584-020-0441-1
10.1107/S0021889808042726
ContentType Journal Article
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References Zhang (ref_22) 2017; 1137
Gao (ref_24) 2019; 1176
Nomura (ref_16) 2019; 9
Smith (ref_2) 2010; 24
Dolomanov (ref_32) 2009; 42
ref_12
Baghernejad (ref_25) 2011; 15
ref_33
ref_10
Childs (ref_26) 2007; 4
Alirezaei (ref_7) 2017; 6
Roubenoff (ref_5) 1990; 16
Pascual (ref_9) 2009; 8
ref_18
Kang (ref_19) 2017; 1130
Martin (ref_34) 2013; 13
Rout (ref_28) 2021; 12
Hilfiker (ref_15) 2006; 1
Sheldrick (ref_31) 2015; 71
Khosravan (ref_1) 2008; 65
Burns (ref_11) 2011; 377
Maddileti (ref_17) 2013; 13
ref_23
Pisaniello (ref_3) 2018; 20
Gao (ref_20) 2021; 2021
Tang (ref_13) 2018; 35
ref_29
Dehlin (ref_4) 2020; 16
ref_27
Newman (ref_14) 2016; 2
ref_8
Sheldrick (ref_30) 2015; 71
ref_6
Han (ref_21) 2016; 11
References_xml – volume: 20
  start-page: 143
  year: 2018
  ident: ref_3
  article-title: Gout prevalence and predictors of urate-lowering therapy use: Results from a population-based study
  publication-title: Arthritis Res. Ther.
  doi: 10.1186/s13075-018-1633-9
– volume: 15
  start-page: 3091
  year: 2011
  ident: ref_25
  article-title: Application of p-toluenesulfonic Acid (PTSA) in Organic Synthesis
  publication-title: Curr. Org. Chem.
  doi: 10.2174/138527211798357074
– volume: 65
  start-page: 355
  year: 2008
  ident: ref_1
  article-title: Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects
  publication-title: Br. J. Clin. Pharmacol.
  doi: 10.1111/j.1365-2125.2007.03016.x
– volume: 71
  start-page: 3
  year: 2015
  ident: ref_31
  article-title: Crystal Structure Refinement with SHELXL
  publication-title: Acta Crystallogr. C Struct. Chem.
  doi: 10.1107/S2053229614024218
– volume: 8
  start-page: 191
  year: 2009
  ident: ref_9
  article-title: Febuxostat
  publication-title: Nat. Rev. Drug Discov.
  doi: 10.1038/nrd2831
– volume: 1176
  start-page: 633
  year: 2019
  ident: ref_24
  article-title: A new febuxostat imidazolium salt hydrate: Synthesis, crystal structure, solubility, and dissolution study
  publication-title: J. Mol. Struct.
  doi: 10.1016/j.molstruc.2018.08.098
– volume: 1
  start-page: 1
  year: 2006
  ident: ref_15
  article-title: Relevance of solid-state properties for pharmaceutical products
  publication-title: Polymorph. Pharm. Ind.
– volume: 1130
  start-page: 480
  year: 2017
  ident: ref_19
  article-title: Syntheses, structure characterization and dissolution of two novel cocrystals of febuxostat
  publication-title: J. Mol. Struct.
  doi: 10.1016/j.molstruc.2016.10.044
– volume: 4
  start-page: 323
  year: 2007
  ident: ref_26
  article-title: The salt−cocrystal continuum: The influence of crystal structure on ionization state
  publication-title: Mol. Pharm.
  doi: 10.1021/mp0601345
– volume: 13
  start-page: 4295
  year: 2013
  ident: ref_34
  article-title: Ketoconazole salt and co-crystals with enhanced aqueous solubility
  publication-title: Cryst. Growth Des.
  doi: 10.1021/cg400638g
– ident: ref_23
  doi: 10.3390/cryst8020085
– volume: 71
  start-page: 3
  year: 2015
  ident: ref_30
  article-title: IUCr SHELXT–Integrated Space-Group and Crystal-Structure Determination
  publication-title: Acta Crystallogr.
– volume: 12
  start-page: 2954
  year: 2021
  ident: ref_28
  article-title: Recent advances in pharmaceutical cocrystals: From bench to market
  publication-title: Front. Pharmacol.
– volume: 35
  start-page: 454
  year: 2018
  ident: ref_13
  article-title: Preparation, optimisation, and in vitro–in vivo evaluation of febuxostat ternary solid dispersion
  publication-title: J. Microencapsul.
  doi: 10.1080/02652048.2018.1526339
– volume: 377
  start-page: 165
  year: 2011
  ident: ref_11
  article-title: Gout therapeutics: New drugs for an old disease
  publication-title: Lancet
  doi: 10.1016/S0140-6736(10)60665-4
– ident: ref_18
  doi: 10.3390/cryst7120365
– volume: 6
  start-page: 297
  year: 2017
  ident: ref_7
  article-title: An update on allopurinol and kidney failure; new trend for an old drug
  publication-title: J. Renal Inj. Prev.
  doi: 10.15171/jrip.2017.57
– volume: 16
  start-page: 539
  year: 1990
  ident: ref_5
  article-title: Gout and hyperuricemia
  publication-title: Rheum. Dis. Clin. North Am.
  doi: 10.1016/S0889-857X(21)00887-5
– ident: ref_6
– ident: ref_8
– volume: 24
  start-page: 811
  year: 2010
  ident: ref_2
  article-title: Epidemiology of gout: An update
  publication-title: Best Pract. Res. Clin. Rheumatol.
  doi: 10.1016/j.berh.2010.10.004
– ident: ref_29
– ident: ref_33
– ident: ref_27
– ident: ref_12
– ident: ref_10
– volume: 2021
  start-page: 3834368
  year: 2021
  ident: ref_20
  article-title: Cocrystallization of Febuxostat with Pyridine Coformers: Crystal Structural and Physicochemical Properties Analysis
  publication-title: J. Chem.
  doi: 10.1155/2021/3834368
– volume: 13
  start-page: 3188
  year: 2013
  ident: ref_17
  article-title: Soluble cocrystals of the xanthine oxidase inhibitor febuxostat
  publication-title: Cryst. Growth Des.
  doi: 10.1021/cg400583z
– volume: 1137
  start-page: 328
  year: 2017
  ident: ref_22
  article-title: Simultaneous enhancements of solubility and dissolution rate of poorly water-soluble febuxostat via salts
  publication-title: J. Mol. Struct.
  doi: 10.1016/j.molstruc.2017.02.052
– volume: 11
  start-page: 715
  year: 2016
  ident: ref_21
  article-title: Preparation, optimization and in vitro–in vivo investigation for capsules of the choline salt of febuxostat
  publication-title: Asian J. Pharm. Sci.
  doi: 10.1016/j.ajps.2016.05.009
– volume: 9
  start-page: 17314
  year: 2019
  ident: ref_16
  article-title: Febuxostat, a Xanthine Oxidoreductase Inhibitor, Decreases NLRP3-dependent Inflammation in Macrophages by Activating the Purine Salvage Pathway and Restoring Cellular Bioenergetics
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-019-53965-x
– volume: 2
  start-page: 2
  year: 2016
  ident: ref_14
  article-title: Solid form changes during drug development: Good, bad, and ugly case studies
  publication-title: AAPS Open
  doi: 10.1186/s41120-016-0003-4
– volume: 16
  start-page: 380
  year: 2020
  ident: ref_4
  article-title: Global epidemiology of gout: Prevalence, incidence, treatment patterns and risk factors
  publication-title: Nat. Rev. Rheumatol.
  doi: 10.1038/s41584-020-0441-1
– volume: 42
  start-page: 339
  year: 2009
  ident: ref_32
  article-title: OLEX2: A Complete Structure Solution, Refinement and Analysis Program
  publication-title: J. Appl. Crystallogr.
  doi: 10.1107/S0021889808042726
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Snippet The multi-component solid form of febuxostat (FEB) with p-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization...
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StartPage 836
SubjectTerms Aging
Basicity
Bioavailability
Cooling
Crystal growth
Crystal structure
Crystallization
Crystals
Dissolution
Evaporative cooling
febuxostat
Fourier transforms
FT-IR
High temperature
Infrared spectroscopy
p-toluenesulfonic acid
Pharmaceutical industry
Pharmacokinetics
Relative humidity
Rheumatism
salt/co-crystal
SC-XRD
Solvents
Thermogravimetry
Uric acid
X ray powder diffraction
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Title Febuxostat–p-Toluenesulfonic Acid Multi-Component Crystal: Characterization, Crystal Growth and Elucidation of the Salt/Co-Crystal Nature
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