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The presence of a chiral or chirally perturbed chromophore in the molecule under investigation is a fundamental requirement for the appearance of a circular dichroism (CD) spectrum. For native and for most of the substituted cyclodextrins, this condition is not applicable, because although chiral, cyclodextrins lack a chromophore group and therefore have no characteristic CD spectra over 220 nm. The reason this method can be used is that if the guest molecule has a chromophore group and this is in the right proximity to the cyclodextrin, it becomes chirally perturbed. As a result, the complex will now provide a CD signal, and this phenomenon is called induced circular dichroism (ICD). The appearance of the ICD spectrum is clear evidence of the formation of the complex, and the spectral sign and intensity is a good predictor of the structure of the complex. By varying the concentration of cyclodextrin, the ICD signal changes, resulting in a saturation curve, and from these data, the stability constant can be calculated for a 1:1 complex. This article compares ICD and NMR spectroscopic and molecular modeling results of cyclodextrin complexes of four model compounds: nimesulide, fenbufen, fenoprofen, and bifonazole. The results obtained by the different methods show good agreement, and the structures estimated from the ICD spectra are supported by NMR data and molecular modeling. [ABSTRACT FROM AUTHOR]

The stability of host–guest complexes of two NSAID drugs with similar physicochemical properties, fenbufen and fenoprofen, was investigated by comparing induced circular dichroism and 1H nuclear magnetic resonance methods using eight cyclodextrins of different degrees of substitution and isomeric purity as guest compounds. These cyclodextrins include native β-cyclodextrin (BCyD), 2,6-dimethyl-β-cyclodextrin 50 (DIMEB50), 80 (DIMEB80) and 95% (DIMEB95) isomerically pure versions, low-methylated CRYSMEB, randomly methylated β-cyclodextrin (RAMEB) and 4.5 and 6.3 average substitution grade hydroxypropyl-β-cyclodextrin (HPBCyD). The stability constants obtained by the two methods show good agreement in most cases. For fenbufen complexes, there is a clear trend that the stability constant increases with the degree of substitution while isomer purity has a smaller effect on the magnitude of stability constants. A significant difference was found in the case of DIMEB50 when compared to DIMEB80/DIMEB95, while the latter two are similar. In the fenbufen–fenoprofen comparison, fenbufen, with its linear axis, gives a more stable complex, while fenoprofen shows lower constants and poorly defined trends. [ABSTRACT FROM AUTHOR]

COVID-19 infection is associated with a significant fatality rate in individuals suffering from severe acute respiratory distress syndrome (ARDS). Among the several possibilities, inhibition of hypoxia-inducible factor prolyl hydroxylase-2 or prolyl hydroxylase domain-containing protein 2 (PHD2) in a hypoxia-independent way is a prospective therapeutic target for the treatment of ARDS. Vadadustat, Roxadustat, Daprodustat, Desidustat, and Enarudustat are the available clinical trial inhibitors. This study is proposed to focus on the repurposing of FDA-approved drugs as effective PHD2 inhibitors. This computational study utilises e-pharmacophore hypothesis generation from the native ligand–protein complex (PDB ID: 5OX6) based on XP visualiser information. The hypothesis containing five essential features (AAANR) was incorporated for FDA database screening, followed by Glide XP molecular docking and Prime MM-GBSA binding free energy calculations. Top scored ligands were investigated and Fenbufen was identified as an effective PHD-2 inhibitor by comparing with the native co-crystal ligand (Vadadustat). The manual lead optimisation of the Fenbufen structure was adopted to improve inhibitory potency, by increasing the binding affinity and protein–ligand stability. The newly designed compounds B and C showed additional binding interactions, excellent docking scores, binding free energy, and an acceptable range of ADME properties. Also, Fenbufen and compound C owned preferable protein–ligand stability during MD simulation when compared with the co-crystallised clinical trial ligand. Based on our findings, we deduce that Fenbufen can be proposed as an effective repurposable candidate as its structural modification showed a remarkable improvement in PHD2 inhibition. [ABSTRACT FROM AUTHOR]

The stability of host–guest complexes of two NSAID drugs with similar physicochemical properties, fenbufen and fenoprofen, was investigated by comparing induced circular dichroism and 1H nuclear magnetic resonance methods using eight cyclodextrins of different degrees of substitution and isomeric purity as guest compounds. These cyclodextrins include native β-cyclodextrin (BCyD), 2,6-dimethyl-β-cyclodextrin 50 (DIMEB50), 80 (DIMEB80) and 95% (DIMEB95) isomerically pure versions, low-methylated CRYSMEB, randomly methylated β-cyclodextrin (RAMEB) and 4.5 and 6.3 average substitution grade hydroxypropyl-β-cyclodextrin (HPBCyD). The stability constants obtained by the two methods show good agreement in most cases. For fenbufen complexes, there is a clear trend that the stability constant increases with the degree of substitution while isomer purity has a smaller effect on the magnitude of stability constants. A significant difference was found in the case of DIMEB50 when compared to DIMEB80/DIMEB95, while the latter two are similar. In the fenbufen–fenoprofen comparison, fenbufen, with its linear axis, gives a more stable complex, while fenoprofen shows lower constants and poorly defined trends.

A heterogeneous single-site catalyst Pd@MOF-808 was successfully synthesized by water-based, green synthesis procedure. The catalytic experiments exhibited the Pd@MOF-808 promoted efficiently the Suzuki–Miyaura coupling reaction without the assistance of organic phosphine ligands at atmospheric pressure conditions. The catalyst also could be applied in the gram-scale synthesis of industrially anti-inflanmatory analgestic Fenbufen. [ABSTRACT FROM AUTHOR]

Aim: In the present study, we aimed to investigate the effects of Fenbufen treatment on the SAP model induced by caerulein and lipopolysaccharide., Background: Severe acute pancreatitis (SAP) is an extremely dangerous disease with high mortality, which is associated with inflammatory response and acinar cell death. The caspase family plays an important role in cell death, such as caspase-1 and caspase-11 in pyroptosis. In recent years, caspases have been shown to be a novel pharmacological target of Fenbufen., Objective: Effects of Fenbufen on pancreatic tissue damage and serum levels of lipase and amylase in SAP in mice; Effect of Fenbufen on caspase-1 pathway in SAP in mice; Effect of Fenbufen on caspase-1/caspase-11-mediated pyroptosis of PACs in SAP in mice; Effect of Fenbufen on isolated PACs and caspase-1/caspase-11-mediated pyroptosis in vitro., Methods: In vivo, eighteen female C57BL/6 mice were randomly divided into 3 groups: the NC group, the SAP group, and the Fenbufen +SAP group with 6 mice in each group. The SAP model was induced by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes in pancreatic and the serum levels of lipase and amylase and the relative gene and protein expressions in each group were compared. In vitro, pancreatic acinar cells were assigned to 5 groups: medium group, SAP group, Fenbufen 100μM group, Fenbufen 200μM group, and Fenbufen 400μM group. The cell damage and the relative gene and protein expressions in each group were evaluated., Results: Our results showed that Fenbufen ameliorated the severity of SAP and decreased the serum levels of lipase and amylase. Meanwhile, the in vivo and in vitro data demonstrated that Fenbufen inhibited the activation of caspase-1 and caspase-11, decreasing the levels of IL-1β, IL-18, and GSDMD. In in vitro experiments, we found that by inhibiting the activation of caspase-1 and caspase-11, Fenbufen significantly reduced lactate dehydrogenase (LDH) excretion by acinar cells., Conclusion: In general, our data showed that Fenbufen could protect the pancreatic acinar cell from injury by inhibiting pyroptosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The presence of a chiral or chirally perturbed chromophore in the molecule under investigation is a fundamental requirement for the appearance of a circular dichroism (CD) spectrum. For native and for most of the substituted cyclodextrins, this condition is not applicable, because although chiral, cyclodextrins lack a chromophore group and therefore have no characteristic CD spectra over 220 nm. The reason this method can be used is that if the guest molecule has a chromophore group and this is in the right proximity to the cyclodextrin, it becomes chirally perturbed. As a result, the complex will now provide a CD signal, and this phenomenon is called induced circular dichroism (ICD). The appearance of the ICD spectrum is clear evidence of the formation of the complex, and the spectral sign and intensity is a good predictor of the structure of the complex. By varying the concentration of cyclodextrin, the ICD signal changes, resulting in a saturation curve, and from these data, the stability constant can be calculated for a 1:1 complex. This article compares ICD and NMR spectroscopic and molecular modeling results of cyclodextrin complexes of four model compounds: nimesulide, fenbufen, fenoprofen, and bifonazole. The results obtained by the different methods show good agreement, and the structures estimated from the ICD spectra are supported by NMR data and molecular modeling.

The facile fabrication of single-walled carbon nanotubes (SWCNTs)-doping molecularly imprinted polymer (MIP) nanocomposite-based binary green porogen system, room-temperature ionic liquids (RTILs), and deep eutectic solvents (DESs) was developed for drug delivery system. With fenbufen (FB) as template molecule, 4-vinylpyridine (4-VP) was used as functional monomer, ethylene glycol dimethacrylate as cross-linking monomer, and 1-butyl-3-methylimidazoliumtetrafluoroborate and choline chloride/ethylene glycol as binary green solvent, in the presence of SWCNTs. The imprinting effect of the SWCNT–MIP composites was optimized by regulation of the amount of SWCNTs, ratio of RTILs and DES, and the composition of DES. Blue shifts of UV bands strongly suggested that interaction between 4-VP and FB can be enhanced due to SWCNT doping in the process of self-assembly. The reinforced imprinted effect of CNT-doping MIP can provide superior controlled release characteristics. Compared with the control MIP prepared without SWCNTs, the imprinting factor of the SWCNT–MIP composites exhibited a twofold increase. In the analysis for the FB release kinetics from all samples, the SWCNT-reinforced MIP produced the lowest value of drug diffusivity. The relative bioavailability of the SWCNT–MIP composites (F %) displayed the highest value of 143.3% compared with the commercial FB tablet, whereas the control MIP and SWCNT–non-MIP composites was only 48.3% and 44.4%, respectively. The results indicated that the SWCNT–MIP nanocomposites developed here have potentials as the controlled-release device. [ABSTRACT FROM AUTHOR]

• A codrug molecular salt of pyrimethamine with fenbufen was designed and prepared. • The accurate structure of the salt was resolved by various techniques. • The dissolubility behavior of the salt was studied theoretically and experimentally. • Both solubility and dissolution rate of pyrimethamine were optimized by the salt formation approach. An approach of dual-drug salt formation assisted increase efficacy has been put forward with the aim of fully exploiting the benefits of NSAID fenbufen (HFB) in enhancing the dissolubility and efficacy of antimalarial drug pyrimethamine (PYR). The approach features the acidic property of HFB and PYR's alkalinity to generate the designed molecular salt via the neutralization reaction, thus making the solubility capacity of the two bulk drugs be concurrently heightened due to the salt formation effect, which, in turn, not only makes for enhancing PYR's bioavailability, but contributes to playing the fast and efficient antipyretic function of HFB serving as a fever-relieving medicine, thereby, conducing to increasing the therapeutic effect of PYR on malaria. Based on this approach, the objective dual-drug molecular salt PYR-HFB has been successfully attained and structurally authenticated by single-crystal X-ray diffraction and diversified analytical techniques. The single-crystal structure analysis demonstrates that the resulting heterodimer entity in the asymmetric unit of the molecular salt comprises a HFB anion and a PYR cation linked by robust charge-assisted hydrogen-bonds to construct an integral 3D supramolecular network, endowing the present molecular salt with the ability to respectively raise solubility and intrinsic dissolution rate up to 2.3- and 4.6-fold relative to parent drug PYR, which fulfills positive connections with theoretical forecasts involving Hirshfeld surface analysis, molecular electrostatic potential, theory of atoms in molecules and frontier molecular orbit. Therefore, this investigation not only affords a fire-new crystalline style with developing foreground for PYR, but supplies an insightful salt formation approach for perfecting both dissolubility and efficiency of antimalarial medicines at the molecular level by playing the characteristic and function of NSAIDs in treating malaria. A dual-drug molecular salt of pyrimethamine (PYR) and fenbufen (HFB) is successfully synthesized and fully characterized. The dissolubility behaviors of the molecular salt are comprehensively investigated by means of theory and experiment approaches, revealing that the solubility and dissolution rate of pyrimethamine have been enhanced simultaneously through the codrug salt formation approach. [Display omitted] [ABSTRACT FROM AUTHOR]

In an attempt to minimize the ulcerogenic potential and associated gastro-intestinal toxicity of bioprecursor fenbufen and its active metabolite biphenyl acetic acid, carrier-linked chimeric derivatives of the latter were designed and synthesized using amino acids as the promoities. DCC coupling method was used for the synthesis of these amides. The chimeras were characterized by IR and 1H NMR. Pharmacological investigations were carried out in animal models for analgesic, anti-inflammatory, anti-arthritic and ulcerogenic activities. The chimeras exhibited high gastro-sparing effect; quick onset and longer duration of analgesia; enhanced/prolonged anti-inflammatory activity and better anti-arthritic effect than fenbufen or biphenyl acetic acid. These derivatives could be useful as a chronotherapy for rheumatoid arthritis due to their prolonged analgesic and anti-inflammatory effects.

A procedure based on solid-phase extraction (SPE) followed by high performance liquid chromatography (HPLC) with PDA detection has been developed for the analysis of multiple drugs in rat plasma. The analytes evaluated were ulifloxacin, fenbufen and felbinac. Eight different solid phase extraction cartridges were tested to evaluate their applicability for the isolation of drugs from rat plasma. Comparison were recovery of different drugs and reproducibility. The samples were analyzed by HPLC using a Kinetex C 18 EVO column and acetonitrile—10 mM ammonium acetate-methanol as the mobile phase under gradient elution conditions. SPE combined with HPLC-PDA allowed the determination of drugs over a linear range of 0.05–15 μg/mL for ulifloxacin while 0.5–50 μg/mL for felbinac and fenbufen, with limit of detection at 0.05 for ulifloxacin and 0.5 for felbinac and fenbufen. Bond Elut Plexa sorbent was found to provide the most effective clean-up, removing the greatest amount of interfering substance and simultaneously ensuring analyte recoveries higher than 93.54% with relative standard deviation (RSD) <10%. The method was applied with good accuracy and precision in the determination of ulifloxacin, fenbufen and felbinac in rat plasma obtained from rats treated with selected drugs. This method permits its application to pharmacokinetic and pharmacodynamic studies of these analytes and will facilitate detailed investigations on the interactions between new fluoroquinolones and fenbufen. [ABSTRACT FROM AUTHOR]

Fenbufen is an arylpropionic acid derivative belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs). Even though fenbufen is considered a safe drug, some adverse reactions including hepatic events have been reported. To investigate whether mitochondrial damage could be involved in the drug induced liver injury (DILI) by fenbufen, the inhibitory effect of fenbufen and its conjugated metabolites on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria was investigated. Fenbufen glucuronide (F-GlcA), fenbufen- N -acetyl cysteine-thioester (F-NAC) and fenbufen- S -glutathione thioester (F-SG) were found to be more potent inhibitors compared to parent fenbufen (F), whereas fenbufen- O- carnitine (F-carn), fenbufen-glycine (F-gly) and fenbufen- N -acetyl lysine amide (F-NAL) were less potent compared to fenbufen. Fenbufen-CoA thioester (F-CoA) was equally potent as fenbufen in inhibiting ATP synthesis. Fenbufen showed time and concentration dependent inhibition of ATP synthesis with K inact of 4.4 min − 1 and K I of 0.88 μM and K inact /K I ratio of 5.01 min − 1 μM − 1 . Data show that fenbufen did not act through opening MPT pore, nor did incubation of mitochondria with reduced GSH and fenbufen show any protective effect on fenbufen mediated inhibition of oxidative phosphorylation. Inclusion of NADPH in mitochondrial preparations with fenbufen did not modulate the inhibitory effects, suggesting no role of CYP mediated oxidative metabolites on the ATP synthesis in isolated mitochondria. The results from the present experiments provide evidence that fenbufen and its metabolites could be involved in mitochondrial toxicity through inhibition of ATP synthesis. [ABSTRACT FROM AUTHOR]

In this work, the combination of two solubilizing agents, methyl-beta-cyclodextrin and Pluronic F68, is proposed and analyzed for a sparingly water soluble drug, fenbufen. Despite the large solubility enhancement achieved, ca. 70-fold, the synergistic effect promoted by the combination of these agents, is only effective over a narrow concentration range, being replaced by a competition between the drug and hydrophobic blocks of the copolymer when the concentration of the latter increases. Moreover, the detailed analysis of the release profiles, resorting to a model dependent approach, shows that the combination of these agents is a strong modulator of the overall profile and also of the total amount of drug that is released. Molecular dynamics simulation indicates a significant change in the cyclodextrin behavior, when alone in solution, situation in which the collapse of the conical structure is relatively frequent, or in the presence of each of the other components, and also shows that copolymer extension is decreased upon introduction of the drug, while there is an increase in extension when the cyclodextrin is added. Inclusion complexes are detected for both drug and copolymer. These play a definite role in solubilization by cyclodextrins, but are also responsible for the competitive behavior observed when polymeric micelles are present. Hydrophobic block copolymers compete with the drug for the cyclodextrin cavity through the formation of polypseudorotaxanes, which in turn modulates drug release. From the fundamental point of view, this work presents an in depth analysis of the molecular behavior in these systems, focusing on the cyclodextrin, inclusion complexes, polymeric micelles and supramolecular systems. [ABSTRACT FROM AUTHOR]

Fenbufen, a member of nonsteroidal antiinflammatory drugs and widely used in the treatment of rheumatoid arthritis was imprinted by utilizing a zwitterionic polymeric format, N-[(phenylenediammonium) maleimidopropane sulfonate] copolymer. Imprinting was carried out by grafting polymer on a photoiniferter modified silica gel via living radical polymerization. Electrostatic interactions along with complementary H-bonding and other hydrophobic interactions inducing additional synergetic effect between the template (fenbufen) and the imprinted surface led to the formation of imprinted sites. Grafted molecularly imprinted polymer (MIP) was characterized by FTIR and surface area measurements besides the recognition, rebinding and selectivity studies. The surface area, pore diameter and pore volume of the MIP are 259.06 m/g, 4.99 nm and 0.32 cm/g, respectively. The MIP was able to selectively and specifically take up fenbufen quantitatively. Hence, a facile, specific and selective technique using surface-grafted specific molecular contours developed for specific and selective uptake of fenbufen in the presence of various interferrants, in different kinds of matrices is presented. [ABSTRACT FROM AUTHOR]

Novel mutual prodrugs of biphenylacetic acid were designed as a promising gastro-protective alternative to fenbufen. Biphenyacetic acid was covalently linked with two non-essential amino acids ( d-phenylalanine and glycine) possessing wound healing, analgesic, and anti-inflammatory properties. The prodrugs exhibited good stability in stomach homogenates while hydrolytic release of biphenylacetic acid was observed in phosphate buffer, small intestinal homogenates, and 80 % human plasma. In vivo behavior of prodrugs on oral administration to Wistar rats demonstrated 33-45 % release of biphenylacetic acid in blood over a period of 24 h indicating passage of intact prodrugs to colon, colonic release of parent drug followed by its absorption through colonic mucosa into systemic circulation. Prodrugs were extensively evaluated for analgesic, anti-inflammatory, anti-arthritic, and ulcerogenic activities. Biochemical, haemetological, histopathological, and radiological studies were also performed. Conversion of bioprecusor fenbufen into mutual carrier-linked prodrugs proved to be promising alternative in terms of reduced ulcerogenic propensity, longer duration of analgesia, enhanced/prolonged anti-inflammatory activity, and superior anti-arthritic effect. These prodrugs could be developed further for chronotherapy of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Abstract: The structure and host–guest interactions in the inclusion complex (179 atoms) of β-cyclodextrin with fenbufen are studied. Fenbufen, the biphenyl derivative γ-oxo-(1,1′-biphenyl)-4-butanoic acid, is a widespread analgesic and non-steroidal anti-inflammatory drug. Its inclusion complex with β-cyclodextrin improves the oral bioavailability and entails fewer side-effects. Optimized molecular structures, atomic net charges and vibrational spectra have been computed for the host and guest molecules, as well as for the inclusion complex. The functional density theory with the B3LYP/3-21+G method/basis set has been applied. The calculated vibrational frequencies have not been scaled, and the simulated spectra have been compared with those obtained experimentally. The host–guest interactions have been investigated in detail. [Copyright &y& Elsevier]

Abstract: This paper examines the comparative performance of different density functional theory (DFT) methods at various basis sets in predicting molecular and vibration spectra of gamma-oxo-[1,1′-biphenyl]-4-butanoic acid (fenbufen). DFT methods including mPW1PW91, HCTH, SVWN, PBEPBE, B3PW91 and B3LYP were investigated. Different basis sets including LANL2DZ, SDD, LANL2MB, CEP-4G, CEP-31G, and CEP-121G were also considered. It is remarkable that the mPW1PW91/LANL2DZ and mPW1PW91/SDD levels are clearly superior to all of the remaining DFT levels in predicting the structure of fenbufen. The calculated results also indicate that SVWN/LANL2DZ level show better performance in the vibration spectra prediction of fenbufen comparing other DFT methods. [Copyright &y& Elsevier]

Abstract: Following different preparation routes, fenbufen has been intercalated in the interlayer space of layered double hydroxides with Mg2+ and Al3+ or Mg2+, Al3+ and Fe3+ in the layers. Well crystallized samples were obtained in most of the cases (intercalation was not observed by reconstruction of the MgAlFe matrix), with layer heights ranging between 16.1 and 18.8Å. The presence of the LDH increases the solubility of fenbufen, especially when used as a matrix. The dissolution rate of the drug decreases when the drug is intercalated, and is even lower in those systems containing iron; release takes place through ionic exchange with phosphate anions from the solution. Preparation of microspheres with Eudragit® S 100 leads to solids with an homogeneous, smooth surface with efficient covering of the LDH surface, as drug release was not observed at pH lower than 7. [ABSTRACT FROM AUTHOR]

The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 for 2009 contains 4027 complete reviews, 1906 protocols for reviews in production, and 11447 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 600,000 randomized controlled trials, and 12,200 cited papers in the Cochrane methodology register. The health technology assessment database contains over 7500 citations. This edition of the Library contains 90 new reviews, of which 19 have potential relevance for practitioners in pain and palliative medicine. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of a series of 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones derived from 4-oxo-4-(biphenyl-4-yl)butanoic acid (fenbufen) is described. The structures of these compounds were supported by IR, 1H NMR, mass spectrometric data and elemental analysis. These compounds were tested for their antiinflammatory, analgesic, ulcerogenic and lipid peroxidation actions. A few compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a fair number of compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action with reduced malondialdehyde (MDA) content, which is one of the byproducts of lipid peroxidation. In vitro COX-1 and COX-2 isozyme inhibition studies were also performed on some of the selected compounds. Compound 4i and 4h were found to be more selective towards COX-2 as indicated by COX-2 selectivity index of 36.06 and 29.05 (COX-2 IC50 =1.5μM and 1.8μM) respectively. [Copyright &y& Elsevier]

A method is described for determination of fenbufen that is based on the chemiluminescence (CL) reaction of the $${\text{Ru}}\left( {{\text{phen}}} \right)_3^{2 + } $$ –cerium(IV)–fenbufen system. An enhanced CL reaction was developed, and optimum conditions for CL were investigated. The CL was linearly dependent on fenbufen concentration in the range 4.0 × 10−8–9.0 × 10−6 mol L−1. The detection limit was 2.0 × 10−8 mol L−1. The relative standard deviation (RSD) was 2.8% for eleven measurements of 6.0 × 10−7 mol L−1 fenbufen standard solution. The new method enables simple, sensitive, and rapid determination of fenbufen and has been used for determination of fenbufen in pharmaceutical preparations in capsule, spiked serum and urine samples. [ABSTRACT FROM AUTHOR]

Abstract: Temperature dependency of saturated vapour pressure for Fenbufen (FBF) was obtained. Heat capacities for Fenbufen, Diflunisal (DIF), and Flurbiprofen (FBP) were measured, and standard thermodynamic functions of sublimation were calculated (FBF: ; ; ; DIF: ; ; ; FBP: ; ; ). Thermochemical parameters of fusion process for FBF were obtained, and evaporation enthalpy was estimated from fusion and sublimation enthalpies. Temperature dependencies of the solubility in buffer solutions (pHs 2.0 and 7.4), n-Octanol, and n-Hexane were measured, and solution and solvation thermodynamic functions were calculated. The transfer thermodynamic functions from n-Hexane to solvents used (imitating specific “drug–solvent” interaction), and from buffer solutions to n-Octanol (imitating partitioning/distribution processes) were analyzed. Specific/non-specific “drug–solvent” interaction ratios in terms of solvation enthalpies were estimated. All studied solutions are characterized by prevalence of non-specific “drug–solvent” interactions. A difference exists between mechanisms of partitioning and distribution of studied drugs. [Copyright &y& Elsevier]

Abstract: Layered double hydroxides (LDHs), or so-called anionic clays, consist of cationic brucite-like layers and exchangeable interlayer anions. Because of their biocompatibility, some LDHs, such as Mg/Al, Zn/Al, Fe/Al and Li/Al-LDH, can be used as host materials for drug-LDH host–guest supramolecular structures. The anti-inflammatory drug fenbufen has been intercalated into layered double hydroxides for the first time by co-precipitation under a nitrogen atmosphere. The product has been characterized by powder X-ray diffraction (XRD), FT-IR spectroscopy, elemental analysis and thermogravimetry (TG) and shows an expanded LDH structure, indicating that the drug has been successfully intercalated into LDH. In addition, the dependence of the nature of the fenbufen intercalation process on conditions such as pH value and chemical composition of the host has been systematically investigated. The interlayer distance in the intercalated materials increases with increasing pH value, resulting from a change in the arrangement of interlayer anions from monolayer to interdigitated bilayer. Drug release characteristics of the pillared LDH materials were investigated by a dissolution test in a simulated intestinal fluid (buffer at pH 7.8). The results show that the drug release of supramolecular LDH materials was a slow process, especially in the case of Mg/Al intercalated materials, suggesting that these drug-inorganic hybrid materials can be used as an effective drug delivery system. [Copyright &y& Elsevier]

The crystal structure of fenbufen was determined by X-ray diffraction techniques. The compound was recrystallized in orthorhombic crystal system, space group Pca2 , a=31.918(10), b=5.550(2), c=15.078(9) Å, D =1.26, D =1.264 g/cm, and Z=8. The structure was solved by direct methods and refined by least-squares procedure to the final R value of 0.051 for 1780 independent reflections. Two molecules in the asymmetric unit are related by a pseudo center of symmetry and dimerized via O−H...O hydrogen bonds. The carbonyl group attached to the phenyl ring is nearly coplanar to the ring. In the crystal the molecules are arranged in parallel stacks in the a direction. [ABSTRACT FROM AUTHOR]

The effects of the non-steroidal anti-inflammatory drugs fenbufen and ibuprofen on hepatic cytochrome P450 activities and peroxisomal proliferation were investigated in the rat, following intraperitoneal administration at three dose levels. At the two highest doses, 30 and 150 mg/kg, ibuprofen stimulated lauric acid hydroxylase activity but no other dose-dependent effects on cytochrome P450 activities were evident. Fenbufen, at the highest dose of 150 mg/kg, decreased cytochrome P450 content and related activities, and this effect was attributed to the toxicity of the drug at this dose. Immunoblot studies employing solubilized microsomes from ibuprofen-treated rats revealed that ibuprofen increased the apoprotein levels of CYP4A1, at the two higher doses. The same treatment with ibuprofen, at the highest dose only, increased the β-oxidation of palmitoyl CoA, determined in liver homogenates, and immunoblott analysis showed an increase in the apoprotein levels of the rans-2-enyol CoA hydratase trifunctional protein. Fenbufen did not influence palmitoyl β-oxidation. Computer graphic overlays with clofibric acid showed that ibuprofen, when compared with fenbufen, displayed a better overall fit to clofibric acid. Finally, interaction energies between the two drugs and the putative peroxisome proliferator-activated receptor lignad domain revealed that ibuprofen had a higher affinity for the receptor than fenbufen, but the difference was modes. It is concluded that ibuprofen, at doses far exceeding those employed clinically, is a weak inducer of both CYP4A1 activity and peroxisomal proliferation and these effects may be attributed to the presence of an aryl propionic acid moiety. These results are discussed with reference to the role of CYP4A induction and peroxisomal proliferation in the hepatotoxicity of this class od drugs. [ABSTRACT FROM AUTHOR]