Characterization and Thermodynamic Relationship of Three Polymorphs of a Xanthine Oxidase Inhibitor, Febuxostat

Patel, Jinish; Jagia, Moksh; Bansal, Arvind K.; Patel, Sarsvatkumar

doi:10.1002/jps.24570

Cited by 18 publications

(10 citation statements)

References 45 publications

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“…From reference [2], the T fus and ∆H fus values for FBX were derived as 486.53 K and 27.58 kJ mol −1 , respectively. Using Equation ( 7), the ∆C p for FBX was estimated to be 56.68 J mol −1 K −1 .…”

Section: Ideal Solubility Of Fbx and Solute-solvent Interactionsmentioning

confidence: 99%

“…Febuxostat (FBX) (molecular structure: Figure 1; IUPAC name: 2-[3-cyano-4-(2-methyl propoxy)phenyl]-4-methylthiazole-5-carboxylic acid) occurs as a white crystalline powder [1,2]. It is a selective nonpurine inhibitor of xanthine oxidoreductase [3].…”

Section: Introductionmentioning

confidence: 99%

“…FBX is a biopharmaceutical classification system (BCS) class II drug with poor solubility in aqueous media and high permeability [2]. Its solubility in water is very poor, which is the main hurdle for its formulation development [9].…”

Section: Introductionmentioning

confidence: 99%

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Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

et al. 2022

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This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.

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Section: Ideal Solubility Of Fbx and Solute-solvent Interactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

et al. 2022

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“…Ltd., Mumbai, India, and was confirmed to be the stable form I of FXT. 22 The coformers, namely, probenecid, adipic acid, and α-ketoglutaric acid (Figure 1; purity > 99.8%), were purchased from Sigma-Aldrich (MO, USA). Acetonitrile (purity > 99%) was purchased from VWR Scientific (PA, USA) and was of analytical or chromatographic grade.…”

Section: ■ Introductionmentioning

confidence: 99%

Role of Structure, Microenvironmental pH, and Speciation To Understand the Formation and Properties of Febuxostat Eutectics

et al. 2019

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Cocrystallization studies were undertaken to improve the solubility of a highly water-insoluble drug, febuxostat (FXT), used in the treatment of gout and hyperuricemia. A liquid-assisted grinding (LAG) method was successfully employed, starting with the screening of various coformers for obtaining cocrystals. However, in this process, three eutectic systems with coformers (probenecid, adipic acid, and α-ketoglutaric acid) were formed. Affinities of the different functional groups to form a hydrogen bond and ΔpK a differences, leading to the eutectic formation, were discussed. The eutectic systems thus formed were further characterized and analyzed using a differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD). Binary thermal phase diagrams were plotted using different ratios of the systems to confirm the formation of eutectics, and pH-dependent solubility studies exhibited a significant decrease in the solubility in comparison to that of the drug for all three eutectic systems. The solubility of FXT reduced from 46.53 μg/mL (pH 5.63) to 46.03 μg/mL, 28.53 μg/mL, and 18.88 μg/mL; 770.58 μg/mL (pH 8.21) to 307.574 μg/mL, 116.63 μg/mL, 113.40 μg/mL; and from 13165.97 μg/mL (pH 10.13) to 1409.737 μg/mL, 854.51 μg/mL, and 1218.99 μg/mL for FXT-probenecid, FXT-adipic acid, and FXT-α-ketoglutaric acid eutectic systems, respectively. Furthermore, the microenvironmental pH studies were carried out to understand the effect of the microenvironment on the solubility of these eutectic systems. The contribution to solubility from lattice and nonlattice forces considering the microenvironment was also discussed.

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“…Such as difference in heat capacity and its correction constant in melting method and not perfectly linear plot of versus 1/ and temperature and solvent dependence of heat of dissolution. The difference can be contributed to the calculation method; the estimation of transition temperature exhibits significant variation depending on the solvent and is not as accurate as one based on the melting data (PATEL et al, 2015). However, it is following expectation for monotropic pair and is higher than the melting temperature of both polymorphs.…”

Section: Explanation In a Variation Of Estimatedmentioning

confidence: 97%

Polymorph screening and solubility characterization of lercanidipine hydrochloride

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Characterization and Thermodynamic Relationship of Three Polymorphs of a Xanthine Oxidase Inhibitor, Febuxostat

Cited by 18 publications

References 45 publications

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

Role of Structure, Microenvironmental pH, and Speciation To Understand the Formation and Properties of Febuxostat Eutectics

Polymorph screening and solubility characterization of lercanidipine hydrochloride

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