Ketoprofen Molecules Research Articles

Electron Spin Resonance Spectrum Simulations of Possible Radicals of the Ketoprofen Molecule

In this study, the molecular structure of Ketoprofen molecule, which is the drug active ingredient , was revealed by using the Density Functional Theory method and the Molecular Mechanical Force Field method. First of all, conformational space scanning in the Ketoprofen molecule was performed by the Molecular Mechanical Force Field method. The most stable structure of the ketoprofen molecule was found with the help of the Density Functional Theory method. The geometry parameters of the ketoprofen molecule and the Nuclear Magnetic Resonance parameters were calculated with the help of the Density Functional Theory method. Possible radicals were modeled using the most stable structure of the ketoprofen molecule. Electron Spin Resonance parameters of these possible radicals were calculated with the Density Functions Theory method. The calculated Electron Spin Resonance parameters were used in the JEOL IsoSimu/Fa Version 2.2.0 simulation program and theoretical Electron Spin Resonance spectra of possible radicals were obtained.

Sol–Gel Synthesis, Thermal Characterization, Surface Interactions, and Release Kinetics of Silica/Drug Hybrid System

AbstractControlled and local drug delivery systems of anti‐inflammatory agents are attracting increasing attention thanks to their possible pharmaceutical and biomedical applications. These systems have extended therapeutic effects and reduced side effects.The aim of this work is to synthesize a system composed of SiO2 glass and ketoprofen, an anti‐inflammatory drug, by the sol–gel process. Two different percentages (5 and 15 wt%) of drug are entrapped in the silica matrix via the sol–gel method and the dried material are analyzed via Fourier transform infrared spectroscopy (FTIR) and simultaneous Differential Scanning Calorimetery/Thermogravimetric analysis (DSC/TGA). The drug release kinetics of the amorphous bioactive materials are investigated. Molecular Mechanics and Molecular Dynamics simulations are currently in progress to investigate possible interactions between the silica‐based surface and the ketoprofen molecules both at low and high concentration for comparison with experimental data.

Surface Interactions between Ketoprofen and Silica-Based Biomaterials as Drug Delivery System Synthesized via Sol-Gel: A Molecular Dynamics Study.

Biomaterial-based drug delivery systems for a controlled drug release are drawing increasing attention thanks to their possible pharmaceutical and biomedical applications. It is important to control the local administration of drugs, especially when the drug exhibits problems diffusing across biological barriers. Thus, in an appropriate concentration, it would be released in situ, reducing side effects due to interactions with the biological environment after implantation. A theoretical study based on Molecular Mechanics and Molecular Dynamics methods is performed to investigate possible surface interactions between the amorphous SiO2 surface and the ketoprofen molecules, an anti-inflammatory drug, considering the role of drug concentration. These theoretical results are compared with experimental data obtained by analyzing, through Fourier transform infrared spectroscopy (FT-IR), the interaction between the SiO2 amorphous surface and two percentages of the ketoprofen drug entrapped in a silica matrix obtained via the sol–gel method and dried materials. The loaded drug in these amorphous bioactive material forms hydrogen bonds with the silica surface, as found in this theoretical study. The surface interactions are essential to have a new generation of biomaterials not only important for biocompatibility, with specific structural and functional properties, but also able to incorporate anti-inflammatory agents for release into the human body.

Development of activated carbon from Schizolobium parahyba (guapuruvu) residues employed for the removal of ketoprofen

Schizolobium parahyba species can be found in all of South America, producing several residues that can be a major opportunity to develop activated carbon. This work presents the investigation regarding the development of a high specific surface activated carbon (981.55 m2g-1) and its application in the adsorption of ketoprofen from the aqueous media. The ketoprofen molecules were better adhered to the adsorbent surface under acidic conditions (pH = 2), being the ideal adsorbent dosage determined as 0.7g L-1, resulting in satisfactory values. It was found that the system reached equilibrium in 200 to 250min depending on the initial concentration studied, achieving an adsorption capacity of 229mgg-1. The general order was the most suitable model for describing the experimental data, with an R2 ≥ 0.9985 and MSR ≤ 63.40 (mg g-1)2. The equilibrium adsorption found that the temperature increases the adsorption capacity, achieving 447.35mgg-1 at 328K. Besides that, the Tóth model was the most suitable for describing the isotherms R2 ≥ 0.9990 and MSR ≤ 25.67 (mg g-1)2, indicating a heterogeneous adsorbent. The thermodynamic values found that the adsorption of ketoprofen is spontaneous (average ΔG0 of - 32.79kJmol-1) and endothermic (ΔH0 10.44kJmol-1). The treatment of simulated effluent with the developed adsorbent was efficient, removing 90% of ketoprofen, ibuprofen, and salts. It was found that the adsorbent is reaming its adsorption capacity up to the 5th cycle, progressively decreasing the adsorption capacity until the adsorption does not occur past the 12th cycle. Overall, the results demonstrated that the activated carbon from residual biomass of the Schizolobium parahyba species could be an excellent alternative in obtaining an effective adsorbent to treat wastewater-containing drugs.

Experimental and theoretical studies of the interaction of ketoprofen in halloysite nanotubes

In recent years, the application of halloysite (HAL) in the conception of drug systems has become important due to its excellent physicochemical properties. Ketoprofen (KET) is widely used around the world as an anti-inflammatory drug. A formulation of HAL-KET was prepared. The interaction between the KET molecules and HAL has been investigated experimentally by Zeta potential, TEM, XRD, FTIR spectroscopy and TGA/DSC. In addition, this interaction was studied theoretically by using Monte-Carlo calculation method (MC). The results have shown that the interaction of KET is stabilized not only by electrostatic interactions and hydrogen bonds with HAL but also via the delocalized π electrons density of phenyl groups of KET and the hydrogen atoms of HAL.

Solubility Advantage of Amorphous Ketoprofen. Thermodynamic and Kinetic Aspects by Molecular Dynamics and Free Energy Approaches.

Thermodynamic and kinetic aspects of crystalline (c-KTP) and amorphous (a-KTP) ketoprofen dissolution in water have been investigated by molecular dynamics simulation focusing on free energy properties. Absolute free energies of all relevant species and phases have been determined by thermodynamic integration on a novel path, first connecting the harmonic to the anharmonic system Hamiltonian at low T and then extending the result to the temperature of interest. The free energy required to transfer one ketoprofen molecule from the crystal to the solution is in fair agreement with the experimental value. The absolute free energy of the amorphous form is 19.58 kJ/mol higher than for the crystal, greatly enhancing the ketoprofen concentration in water, although as a metastable species in supersaturated solution. The kinetics of the dissolution process has been analyzed by computing the free energy profile along a reaction coordinate bringing one ketoprofen molecule from the crystal or amorphous phase to the solvated state. This computation confirms that, compared to the crystal form, the dissolution rate is nearly 7 orders of magnitude faster for the amorphous form, providing one further advantage to the latter in terms of bioavailability. The problem of drug solubility, of great practical importance, is used here as a test bed for a refined method to compute absolute free energies, which could be of great interest in biophysics and drug discovery in particular.

Роль противовоспалительной терапии в лечении острого и хронического простатита. Особенности инновационной молекулы кетопрофена

Роль противовоспалительной терапии в лечении острого и хронического простатита. Особенности инновационной молекулы кетопрофена

Investigation of Drug for Pulmonary Administration-Model Pulmonary Surfactant Monolayer Interactions Using Langmuir-Blodgett Monolayer and Molecular Dynamics Simulation: A Case Study of Ketoprofen.

Pulmonary administration is widely used for the treatment of lung diseases. The interaction between drug molecules and pulmonary surfactants affects the efficacy of the drug directly. The location and distribution of drug molecules in a model pulmonary surfactant monolayer under different surface pressures can provide vivid information on the interaction between drug molecules and pulmonary surfactants during the pulmonary administration. Ketoprofen is a nonsteroidal anti-inflammatory drug for pulmonary administration. The effect of ketoprofen molecules on the lipid monolayer containing 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-glycerol (DPPG) is studied by surface pressure (π)-area (A) isotherms and compressibility modulus (Cs-1)-surface pressure (π) isotherms. The location and distribution of ketoprofen molecules in a lipid monolayer under different surface pressures are explored by surface tension, density profile, radial distribution function (RDF), and the potential of mean force (PMF) simulated by molecular dynamics (MD) simulation. The introduction of ketoprofen molecules affects the properties of DPPC/DPPG monolayers and the location and distribution of ketoprofen molecules in monolayers with various surface pressures. The existence of ketoprofen molecules hinders the formation of liquid-condensed (LC) films and decreases the compressibility of DPPC/DPPG monolayers. The location and distribution of ketoprofen molecules in the lipid monolayer are affected by cation-π interaction between the choline group of lipids and the benzene ring of ketoprofen, the steric hindrance of the lipid head groups, and the hydrophobicity of ketoprofen molecule itself, comprehensively. The contact state of lipid head group with water is determined by surface pressure, which affects the interaction between drug molecules and lipids and further dominates the location and distribution of ketoprofen in the lipid monolayer. This work confirms that ketoprofen molecules can affect the property and the inner structure of DPPC/DPPG monolayers during breathing. Furthermore, the results obtained using a mixed monolayer containing two major pulmonary surfactants DPPC/DPPG and ketoprofen molecules will be helpful for the in-depth understanding of the mechanism of inhaled administration therapy.

Selected pharmaceuticals removal using algae derived porous carbon: experimental, modeling and DFT theoretical insights.

Porous carbon from Laminaria digitata algae activated using NaOH (PCLD@NaOH) was prepared by a chemical activation approach and has been tested for the adsorption of ketoprofen and aspirin molecules. The prepared PCLD@NaOH was characterized using XPS, FTIR, Raman, N2-physisorption, SEM, acidic/basic character (Boehm), and pHPZC. The batch adsorption of ketoprofen and aspirin was investigated under different parameters. The adsorption kinetics on PCLD@NaOH were well described by the Avrami-fractional kinetic model and the equilibrium data by Liu isotherm model. The adsorption capacity of aspirin (970.88 mg g−1 at 25 °C) was higher than ketoprofen (443.45 mg g−1 at 25 °C). The thermodynamic values indicate that the adsorption of ketoprofen and aspirin is exothermic and spontaneous. These results were in good agreement with DFT calculation that shows that the aspirin molecule presents high reactivity, electrophilicity, and softness compared to the ketoprofen molecule. Finally, the response surface methodology was used to optimize the removal efficiency of ketoprofen and aspirin.

Cross-linked and hydrophobized hyaluronic acid-based controlled drug release systems

This work demonstrates the preparation, structural characterization, and the kinetics of the drug release of hyaluronic acid (HyA)-based colloidal drug delivery systems which contain hydrophobic ketoprofen (KP) as model molecule. Because of the highly hydrophilic character of HyA the cross-linked derivatives at different cross-linking ratio have been synthesized. The hydrophobized variants of HyA have also been produced by modifying the polymer chains with cetyltrimethylammonium bromide (CTAB) at various HyA/CTAB ratios. Due to modifications the coherent structure of HyA changes into an incoherent colloidal system that were verified by rheological investigations. Nearly 70% of the encapsulated KP dissolve from the totally cross-linked HyA carrier but the release rate of KP is about 20% (after 8 h) from the CTAB-modified colloidal system at HyA monomer/CTAB 1:0.8 mass ratio. It has been verified that the modified HyA may be a potential candidate for controlled drug release of hydrophobic KP molecules.

Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

Diclofenac is the world known nonsteroidal anti-inflammatory drug (NSAID) predicted before its syntesis on the basis of the model COX enzyme. Due to its specific structural properties the drug possesses high reactivity and outstanding tolerability. Among the key features defining the diclofenac structure is intramolecular N-H ⋯O hydrogen bond confirmed during the X-ray analysis. In the present research we use static DFT calculations, the Quantum Theory of Atoms in Molecules and non-covalent interactions (NCI) index to confirm the additional intramolecular interactions, which influence the drug molecular structure. We focus on the structural stability of diclofenac as the result of the hydrogen bonds breaking/formation at finite temperature utilizing ab initio molecular dynamics simulations. The lifetime of different intramolecular hydrogen bonds is estimated. We perform also the comparative analysis of the structural stability of ibuprofen and ketoprofen molecules in the gas phase at 300 K with respect to diclofenac in terms of the NSAID inhibition activity. Due to the detailed description of diclofenac intramolecular interactions, possible drug modifications for its enhanced water solubility can be suggested.

Ultrafast time resolved spectroscopic studies on the generation of the ketyl-sugar biradical by intramolecular hydrogen abstraction among ketoprofen and purine nucleoside dyads.

Intramolecular hydrogen abstraction reactions among ketoprofen (KP) and purine nucleoside dyads have been proposed to form ketyl-sugar biradical intermediates in acetonitrile. Femtosecond transient absorption studies on KP and purine nucleoside dyads reveal that the triplet state of the KP moiety of the dyads with cisoid structure decay faster (due to an intramolecular hydrogen abstraction reaction to produce a ketyl-sugar biradical intermediate) than the triplet state of the KP moiety of the dyads with transoid structure detected in acetonitrile solvent. For the cisoid 5-KP-dG dyad, the triplet state of the KP moiety decays too fast to be observed by ns-TR(3); only the ketyl-sugar biradical intermediates are detected by ns-TR(3) in acetonitrile. For the cisoid 5-KP-dA dyad, the triplet states of the KP moiety could be observed at early nanosecond delay times, and then it quickly undergoes intramolecular hydrogen abstraction to produce a ketyl-sugar biradical intermediate. For the cisoid 5-KPGly-dA and transoid 3-KP-dA dyads, the triplet state of the KP moiety had a longer lifetime due to the long distance chain between the KP moiety and the purine nucleoside (5-KPGly-dA) and the transoid structure (3-KP-dA). The experimental and computational results suggest that the ketyl-sugar biradical intermediate is generated with a higher efficiency for the cisoid dyad. However, the transoid dyad exhibits similar photochemistry behavior as the KP molecule, and no ketyl-sugar biradical intermediate was observed in the ns-TR(3) experiments for the transoid 3-KP-dA dyad.

Characterization and skin permeation of ketoprofen-loaded vesicular systems

PurposeTo determine the effect of elasticity on the skin permeation of ketoprofen from surfactant-based vesicular formulations and elastic liposomes. MethodsKetoprofen-loaded surfactant-based vesicles and elastic liposomes were prepared by sonication. Citric buffer (at pH 3.0) was used as rehydration buffer. Characterization studies of the prepared liposomal formulations were performed by dynamic light scattering, extrusion, and 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. Ketoprofen transport studies across human skin were performed for all formulations. ResultsStable ketoprofen-loaded formulations were prepared. Addition of an edge activator, in the absence of the drug, increased the elasticity of the vesicles and liposomes. Ketoprofen loading reduced the elasticity of the liposomes and surfactant-based-vesicles. However, at saturation, the elasticity was still higher than that in the absence of the edge activator and ketoprofen, except for ketoprofen-loaded liposomes with Span 80. NMR studies revealed that the ketoprofen molecules were entrapped in a vesicle bilayer in all vesicular formulations and that the ketoprofen molecules affected the phosphate mobility in the liposomal formulations. Ketoprofen transport studies across human skin clearly showed that the surfactant-based vesicular formulations were superior to the elastic liposomal formulations. ConclusionSurfactant-based vesicles enhance ketoprofen transport across human skin, while no enhancement of ketoprofen was observed when loaded in elastic liposomes.

Zero-order drug release cellulose acetate nanofibers prepared using coaxial electrospinning

Novel drug-loaded cellulose acetate (CA) nanofibres were prepared by a modified coaxial electrospinning process, after which their zero-order drug release profiles were determined. Using 2 % (w/v) unspinnable CA solution as a sheath fluid, coaxial electrospinning can be conducted smoothly to generate ketoprofen (KET)-loaded CA nanofibres coated with a thin layer of blank CA. Scanning electron microscopy images demonstrated that nanofibres obtained from the modified coaxial process have a smaller average diameter, a narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single-fluid electrospinning. Transmission electron microscopy observations demonstrated that the nanofibres have a thin coating layer of blank CA on their surface with a thickness of ca. 15 nm. X-ray diffraction and differential scanning calorimetry verified that KET molecules in all of the nanofibres presented an amorphous state. Fourier transform infrared spectra demonstrated that CA has good compatibility with KET, which is brought about by hydrogen bonding. In vitro dissolution tests showed that the nanofibres coated with blank CA have no initial burst release effects and can provide a zero-order drug release profile over 96 h via a diffusion mechanism. The modified coaxial electrospinning method can provide new approaches in developing cellulose-based nano products with definite structural characteristics and improved functional performance.

Adsorption of clofibric acid and ketoprofen onto powdered activated carbon: Effect of natural organic matter

The adsorption of two acidic pharmaceutically active compounds (PhACs), clofibric acid and ketoprofen, onto powdered activated carbon (PAC) was investigated with a particular focus on the influence of natural organic matter (NOM) on the adsorption of the PhACs. Suwannee River humic acids (SRHAs) were used as a substitute for NOM. Batch adsorption experiments were conducted to obtain adsorption kinetics and adsorption isotherms with and without SRHAs in the system. The adsorption isotherms and adsorption kinetics showed that the adsorption of clofibric acid was not significantly affected by the presence of SRHAs at a concentration of 5 mg (as carbon) L−1. An adsorption capacity of 70 to 140 mg g−1 was observed and equilibrium was reached within 48 h. In contrast, the adsorption of ketoprofen was markedly decreased (from about 120 mg g−1 to 70–100 mg g−1) in the presence of SRHAs. Higher initial concentrations of clofibric acid than ketoprofen during testing may explain the different behaviours that were observed. Also, the more hydrophobic ketoprofen molecules may have less affinity for PAC when humic acids (which are hydrophilic) are present. The possible intermolecular forces that could account for the different behaviour of clofibric acid and ketoprofen adsorption onto PAC are discussed. In particular, the relevance of electrostatic forces, electron donor-acceptor interaction, hydrogen bonding and London dispersion forces are discussed

Anodic oxidation of ketoprofen—An anti-inflammatory drug using boron doped diamond and platinum electrodes

The mineralization of ketoprofen (KP) by anodic oxidation was studied by employing boron doped diamond (BDD) and Pt electrodes. The redox behavior of KP molecule, fouling of electrodes, generation of oxygen and active chlorine species were studied by cyclic voltammetry. The effect of electrolyte, pH of aqueous medium and applied current density on the mineralization behavior of KP was also investigated. The degradation and mineralization were monitored by UV–vis spectrophotometer and total organic carbon analyzer, respectively. The results were explained in terms of in situ generation of hydroxyl radical ( OH), peroxodisulfate (S 2O 8 2−), and active chlorine species (Cl 2, HOCl, OCl −). The physisorbed OH on BDD was observed to trigger the combustion of KP in to CO 2 and H 2O. The poor mineralization at both BDD and Pt anodes in the presence of NaCl as supporting electrolyte was ascribed to the formation of chlorinated organic compounds which are refractory. Complete mineralization of KP molecule was achieved using Na 2SO 4 as supporting electrolyte.

Drug–excipient interactions in ketoprofen: A vibrational spectroscopy study

Ketoprofen (3-benzoyl-alpha-methylbenzeneacetic acid) is a widely used nonsteroidal anti-inflammatory drug (NSAID), always administered in the form of drug-excipient physical mixtures (PMs). The occurrence of possible interactions between ketoprofen and two commonly used excipients-lactose (LAC) and polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence of drug:excipient close contacts, which were enhanced by aging, was verified for the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS. These interactions were found to involve mainly the central carbonyl and the terminal methyl-carboxylic moieties of the ketoprofen molecule, this being reflected in particular vibrational modes, such as the methyl torsion, the out-of-plane C-OH bending, and the inter-ring C=O stretching.

Conformational study of ketoprofen by combined DFT calculations and Raman spectroscopy

A conformational study of ketoprofen was carried out by both density functional theory (DFT) calculations and Raman spectroscopy. Nine different geometries were found to correspond to energy minimum conformations but only one of them was experimentally detected in the condensed phase spectra. Those rotations which interconvert the five most stable conformers were studied and the intramolecular interactions governing the corresponding conformational preferences were assessed. A thorough vibrational analysis was performed, leading to the assignment of both the solid and liquid spectra. Evidence for formation of intermolecular hydrogen bonds between carboxylic groups of adjacent ketoprofen molecules, leading to dimeric entities, was obtained.

케토프로펜의 경피전달 및 전기삼투압의 영향

We investigated some important factors which affect the transdermal flux of ketoprofen, a nonsteroidal anti-inflammatory agent, as a first step to provide some basic knowledge for the development of a iontophoretic transdermal patch system. Factors such as current density, polarity, buffer (HEPES) and electrolyte concentration and pH were studied using hairless mouse skin. The effect of poly(L-lysin), which is known to affect the electro-osmotic flow through skin, on flux was also studied. Passive flux was about at pH 4.0, but was negligible at pH 7.4 where all ketoprofen molecules dissolved are ionized (ketoprofen pKa=5.94). At pH 4.0, application of anodal current increased the flux further above the passive level, however anodal flux at pH 7.4 was much smaller than passive flux at pH 4.0. The application of cathodal current at pH 4.0 increased the average flux to , depending on the current density applied. At pH 7.4, cathodal flux was only about . Decrease in buffer and electrolyte concentration increased this cathodal flux about 10 fold. However decrease in HEPES buffer concentration 100 fold did not affect the flux. Anodal flux of acetaminophen was much larger than cathodal flux, indicating that electroosmotic flow can be playing an important role in the flux. Poly(L-lysin) increased the cathodal flux at pH 7.4. These results provide some important insights into the mechanism of transdermal flux of ketoprofen and the role of electroosmotic flow.