RESUMO
Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.
Assuntos
Cetoprofeno , Ozônio , Poluentes Químicos da Água , Cetoprofeno/química , Ozônio/química , Poluentes Químicos da Água/química , Cinética , Anti-Inflamatórios não Esteroides/química , Modelos Químicos , Purificação da Água/métodosRESUMO
Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.
Assuntos
Anti-Inflamatórios não Esteroides , Cetoprofeno , Cetorolaco , Ligação Proteica , Albumina Sérica Humana , Humanos , Cetoprofeno/química , Cetoprofeno/metabolismo , Cetoprofeno/farmacocinética , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacocinética , Cetorolaco/química , Cetorolaco/metabolismo , Cetorolaco/farmacocinética , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Dicroísmo Circular , Termodinâmica , Espectrometria de Fluorescência , Sítios de LigaçãoRESUMO
The metastability of amorphous formulations poses barriers to their safe and widespread commercialization. The propensity of amorphous solid dispersions (ASDs) to crystallize is directly linked to their molecular structure. Amorphous structures are inherently complex and thus difficult to fully characterize by experiments, which makes structural simulations an attractive route for investigating which structural characteristics correlate with ASD stability. In this study, we use empirical potential structure refinement (EPSR) to create molecular models of ketoprofen-poly(vinylpyrrolidone) (KTP/PVP) ASDs with 0-75 wt % drug loading. The EPSR technique uses X-ray total scattering measurements as constraints, yielding models that are consistent with the X-ray data. We perform several simulations to assess the sensitivity of the EPSR approach to input parameters such as intramolecular bond rotations, PVP molecule length, and PVP tacticity. Even at low drug loading (25 wt %), â¼40% of KTP molecules participate in KTP-KTP hydrogen bonding. The extent of KTP-PVP hydrogen bonding does not decrease significantly at higher drug loadings. However, the models' relative uncertainties are too large to conclude whether ASDs' lower stabilities at high drug loadings are due to changes in drug-excipient hydrogen bonding or a decrease in steric hindrance of KTP molecules. This study illustrates how EPSR, combined with total scattering measurements, can be a powerful tool for investigating structural characteristics in amorphous formulations and developing ASDs with improved stability.
Assuntos
Cetoprofeno , Povidona , Difração de Raios X , Cetoprofeno/química , Povidona/química , Difração de Raios X/métodos , Cristalização , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Modelos Moleculares , Estabilidade de MedicamentosRESUMO
This study explores the realm of personalized medicine by investigating the utilization of 3D-printed dosage forms, specifically focusing on patient-specific enteric capsules designed for the modified release of ketoprofen, serving as a model drug. The research investigates two distinct scenarios: the modification of drug release from 3D-printed capsules crafted from hydroxypropyl methylcellulose phthalate:polyethylene glycol (HPMCP:PEG) and poly(vinyl alcohol) (PVA), tailored for pH sensitivity and delayed release modes, respectively. Additionally, a novel ketoprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) based on pomegranate seed oil (PSO) was developed, characterized, and employed as a fill material for the capsules. Through the preparation and characterization of the HPMCP:PEG based filament via the hot-melt extrusion method, the study thoroughly investigated its thermal and mechanical properties. Notably, the in vitro drug release analysis unveiled the intricate interplay between ketoprofen release, polymer type, and capsule thickness. Furthermore, the incorporation of ketoprofen into the SNEDDS exhibited an enhancement in its in vitro cylooxygenase-2 (COX-2) inhibitory activity. These findings collectively underscore the potential of 3D printing in shaping tailored drug delivery systems, thereby contributing significantly to the advancement of personalized medicine.
Assuntos
Cápsulas , Liberação Controlada de Fármacos , Emulsões , Cetoprofeno , Medicina de Precisão , Impressão Tridimensional , Cetoprofeno/química , Medicina de Precisão/métodos , Humanos , Emulsões/química , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos/métodos , Preparações de Ação Retardada , Metilcelulose/química , Metilcelulose/análogos & derivados , Álcool de Polivinil/químicaRESUMO
Deep eutectic solvents (DESs) are commonly used in pharmaceutical applications as excellent solubilizers of active substances. This study investigated the tuning of ibuprofen and ketoprofen solubility utilizing DESs containing choline chloride or betaine as hydrogen bond acceptors and various polyols (ethylene glycol, diethylene glycol, triethylene glycol, glycerol, 1,2-propanediol, 1,3-butanediol) as hydrogen bond donors. Experimental solubility data were collected for all DES systems. A machine learning model was developed using COSMO-RS molecular descriptors to predict solubility. All studied DESs exhibited a cosolvency effect, increasing drug solubility at modest concentrations of water. The model accurately predicted solubility for ibuprofen, ketoprofen, and related analogs (flurbiprofen, felbinac, phenylacetic acid, diphenylacetic acid). A machine learning approach utilizing COSMO-RS descriptors enables the rational design and solubility prediction of DES formulations for improved pharmaceutical applications.
Assuntos
Solventes Eutéticos Profundos , Ibuprofeno , Cetoprofeno , Aprendizado de Máquina , Solubilidade , Cetoprofeno/química , Ibuprofeno/química , Solventes Eutéticos Profundos/química , Inibidores de Ciclo-Oxigenase/química , Ligação de Hidrogênio , Solventes/químicaRESUMO
In this work, the study of the new ligand 3,3'-bis[N,N-bis(pyridine-2-ylmethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L) is reported, where a central 2,2'-biphenol (BPH) fluorophore was functionalized at 3,3'-positions with two dipicolylamine (DPA) side arms as receptor units. Following the synthesis and full chemical-physical characterization, the acid-base and Zn2+-coordination abilities of L were investigated through a combination of potentiometric, UV-Vis, fluorescence, NMR, XRD and DFT measurements. The optical properties of the ligand turned out to be strongly dependent on the pH, being straightforwardly associated with the protonation state of the BPH moiety, whereas its peculiar design allowed to form stable mono and dinuclear Zn2+ complexes. In the latter species, the presence of two Zn2+ ions coordinatively unsaturated and placed at close distance to each other, prompted us to test their usefulness as metallo-receptors for two environmental pollutants of great relevance, ibuprofen and ketoprofen. Potentiometric and fluorescence investigations evidenced that these important non-steroidal anti-inflammatory drugs (NSAIDs) are effectively coordinated by the metallo-receptors and, of relevance, both the stability and the fluorescence properties of the resulting ternary adducts are markedly affected by the different chemical architectures of the two substrates. This study aims at highlighting the promising perspectives arising from the use of polyamino phenolic ligands as chemosensors for H+/Zn2+ and other additional anionic targets in their metal-complexed forms.
Assuntos
Aminas , Complexos de Coordenação , Corantes Fluorescentes , Ibuprofeno , Cetoprofeno , Ácidos Picolínicos , Zinco , Zinco/química , Ligantes , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Aminas/química , Ácidos Picolínicos/química , Cetoprofeno/química , Ibuprofeno/química , Água/química , Teoria da Densidade Funcional , Fenóis/química , Espectrometria de Fluorescência , Estrutura Molecular , Modelos Moleculares , SoluçõesRESUMO
The molecular structures of nonsteroidal anti-inflammatory drugs (NSAIDs) vary, but most contain a carboxylic acid functional group (RCOOH). This functional group is known to be related to the mechanism of cyclooxygenase inhibition and also causes side effects, such as gastrointestinal bleeding. This study proposes a new role for RCOOH in NSAIDs: facilitating the interaction at the binding site II of serum albumins. We used bovine serum albumin (BSA) as a model to investigate the interactions with ligands at site II. Using dansyl-proline (DP) as a fluorescent site II marker, we demonstrated that only negatively charged NSAIDs such as ibuprofen (IBP), naproxen (NPX), diflunisal (DFS), and ketoprofen (KTP) can efficiently displace DP from the albumin binding site. We confirmed the importance of RCOO by neutralizing IBP and NPX through esterification, which reduced the displacement of DP. The competition was also monitored by stopped-flow experiments. While IBP and NPX displaced DP in less than 1 s, the ester derivatives were ineffective. We also observed a higher affinity of negatively charged NSAIDs using DFS as a probe and ultrafiltration experiments. Molecular docking simulations showed an essential salt bridge between the positively charged residues Arg409 and Lys413 with RCOO-, consistent with the experimental findings. We performed a ligand dissociation pathway and corresponding energy analysis by applying molecular dynamics. The dissociation of NPX showed a higher free energy barrier than its ester. Apart from BSA, we conducted some experimental studies with human serum albumin, and similar results were obtained, suggesting a general effect for other mammalian serum albumins. Our findings support that the RCOOH moiety affects not only the mechanism of action and side effects but also the pharmacokinetics of NSAIDs.
Assuntos
Anti-Inflamatórios não Esteroides , Ácidos Carboxílicos , Simulação de Acoplamento Molecular , Soroalbumina Bovina , Animais , Bovinos , Humanos , Anti-Inflamatórios não Esteroides/química , Sítios de Ligação , Ácidos Carboxílicos/química , Diflunisal/química , Ibuprofeno/química , Cetoprofeno/química , Ligantes , Naproxeno/química , Ligação Proteica , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismoRESUMO
Ketoprofen (KET), commonly used for inflammation in clinical settings, leads to systemic adverse effects with prolonged use, mitigated by topical administration. Nanotechnology-based cutaneous forms, like films, may enhance KET efficacy. Therefore, this study aimed to prepare and characterize films containing KET nanoemulsions (F-NK) regarding mechanical properties, chemical composition and interactions, occlusive potential, bioadhesion, drug permeation in human skin, and safety. The films were prepared using a κ-carrageenan and xanthan gum blend (2 % w/w, ratio 3: 1) plasticized with glycerol through the solvent casting method. Non-nanoemulsioned KET films (F-K) were prepared for comparative purposes. F-NK was flexible and hydrophilic, exhibited higher drug content and better uniformity (94.40 ± 3.61 %), maintained the NK droplet size (157 ± 12 nm), and was thinner and lighter than the F-K. This film also showed increased tensile strength and Young's modulus values, enhanced bioadhesion and occlusive potential, and resulted in more of the drug in the human skin layers. Data also suggested that nano-based formulations are homogeneous and more stable than F-KET. Hemolysis and chorioallantoic membrane tests suggested the formulations' safety. Thus, the nano-based film is suitable for cutaneous KET delivery, which may improve the drug's efficacy in managing inflammatory conditions.
Assuntos
Cetoprofeno , Nanocompostos , Polissacarídeos Bacterianos , Humanos , Cetoprofeno/farmacologia , Cetoprofeno/química , Carragenina/química , Pele , Nanocompostos/químicaRESUMO
BACKGROUND: Ketoprofen is a nonsteroidal anti-inflammatory drug used for the treatment of acute and chronic pain associated with inflammatory conditions. This study aims to evaluate the in vitro percutaneous absorption of ketoprofen 10% formulated in proprietary anhydrous and aqueous gels using the Franz skin finite dose model. MATERIALS AND METHODS: The anhydrous gel was initially characterized for cytotoxicity using EpiDerm skin tissue model by cell proliferation assay and Western blot analysis. The Ultra Performance Liquid Chromatography method for measuring ketoprofen was validated and the stability of ketoprofen 10% in the anhydrous gel formulation was evaluated at 5°C and 25°C for 181 days. The percutaneous absorption of ketoprofen was determined using donated human skin. The tissue sections were mounted within Franz diffusion cells. A variable finite dose of each ketoprofen formulation in either anhydrous or aqueous gel was applied to the skin sections and receptor solutions were collected at various time points. RESULTS: Cell proliferation assay showed minimal cell death when EpiDerm skin tissue was exposed to the anhydrous gel for 24 h; the levels of protein markers of cell proliferation were not affected after 17-h exposure. Ketoprofen was stable in the anhydrous gel when stored at 5°C and 25°C. When compounded in the anhydrous and aqueous gels, ketoprofen had mean flux rate of 2.22 and 2.50 µg/cm2 /h, respectively, after 48 h. The drug was distributed to the epidermis and dermis sections of the skin. Both the anhydrous and aqueous gels facilitated the percutaneous absorption of ketoprofen without statistically significant differences. CONCLUSION: The anhydrous gel can be used as a base to facilitate the transdermal delivery of ketoprofen. Although the anhydrous and aqueous gels can deliver a similar amount of ketoprofen, the anhydrous gel (water activity below 0.6) allows for extended default beyond-use-date of compounding preparations.
Assuntos
Cetoprofeno , Humanos , Cetoprofeno/química , Cetoprofeno/metabolismo , Absorção Cutânea , Pele/metabolismo , Anti-Inflamatórios não Esteroides , Administração Cutânea , Géis , Água/metabolismoRESUMO
The aim was to investigate eutectic transition during tableting and storage. Mixtures of lidocaine and series of NSAIDs with increasing melting point were used as model systems to guide formulators to scaleup eutectic forming materials gaining enhanced dissolution while avoiding deleterious physical changes. Physical mixtures of NSAIDs with lidocaine were prepared at eutectic forming ratio. These were directly compressed, dry co-ground before compression, or compressed after wet granulation. Dissolution of tablets was compared to corresponding dry co-ground mixture. Thermograms of direct compressed tablet were compared to co-ground mixture and pure compound. Stability of direct compressed tablets was assessed. Tableting initiated eutexia which enhanced dissolution of NSAIDs. Eutexia was associated with tablet softening in case of low melting point ketoprofen and aceclofenac. Wet granulation hastened eutexia developing unacceptable tablet in case ketoprofen and aceclofenac. Tablets prepared by direct compression of physical mixtures underwent gradual eutectic transition upon storage with the magnitude of eutectic transition reducing with increased melting point of NSAIDs. Ketoprofen was physically unstable but aceclofenac degraded chemically as well. Tenoxicam and meloxicam tablets were physically and chemically stable. Direct compression after physical mixing is the best tableting technique, but low melting point drugs should consider different strategy before compression.
Assuntos
Diclofenaco/análogos & derivados , Cetoprofeno , Cetoprofeno/química , Anti-Inflamatórios não Esteroides/química , Comprimidos , Lidocaína , SolubilidadeRESUMO
In order to solubilize poorly soluble active pharmaceutical ingredients, various strategies have been implemented over the years, including the use of nanocarriers, such as cyclodextrins and liposomes. However, improving a drug's apparent solubility does not always translate to enhanced bioavailability. This work aimed to investigate to which extent complexation with cyclodextrins and incorporation into liposomes influence drug in vitro permeability and to find a mechanistic description of the permeation process. For this purpose, we investigated hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and phosphatidylcholine liposomes formulations of three chemically diverse compounds (atenolol, ketoprofen and hydrocortisone). We studied drug diffusion of the formulations by UV-localized spectroscopy and advanced data fitting to extract parameters such as diffusivity and bound-/free drug fractions. We then correlated this information with in vitro drug permeability obtained with the novel PermeaPadâ barrier. The results showed that increased concentration of HP-ß-CD leads to increased solubilization of the poorly soluble unionized ketoprofen, as well as hydrocortisone. However, this net increment of apparent solubility was not proportional to the increased flux measured. On the other hand, normalising the flux over the empirical free drug concentration, i.e., the free fraction, gave a meaningful absolute permeability coefficient. The results achieved for the liposomal formulation were consistent with the finding on cyclodextrins. In conclusion, we proved the adequacy and usefulness of our method for calculating free drug fractions in the examined enabling formulations, supporting the validity of the established drug diffusion/permeation theory that the unbounded drug fraction is the main driver for drug permeation across a membrane.
Assuntos
Ciclodextrinas , Cetoprofeno , beta-Ciclodextrinas , Ciclodextrinas/química , Lipossomos/química , 2-Hidroxipropil-beta-Ciclodextrina , beta-Ciclodextrinas/química , Cetoprofeno/química , Hidrocortisona/química , PermeabilidadeRESUMO
The purpose of this study was to combine carbon nanotube with ethosomes in order to obtain hybrid nanocarriers for transdermal delivery of ketoprofen (KP). KP-loaded functionalized single-walled carbon nanotube (f-SWCNTs) composite ethosomes (f-SWCNTs-KP-ES) were designed and were verified by a series of characterizations. The particle size of the preparation is less than 400 nm. DSC and XRD experiments showed that KP existed in an amorphous state after it was adsorbed and loaded on f-SWCNTs. TEM experiments showed that the structure of SWCNTs remained intact after oxidation and modification by PEI. FTIR results showed that PEI were successfully modified on the surface of SWCNT-COOH, and KP was successfully loaded on f-SWCNTs. In vitro release characteristics showed that the preparation had sustained release behavior and conformed to the first-order kinetic equation model. In addition, f-SWCNTs-KP-ES gel were prepared and in vitro skin permeation and in vivo pharmacokinetics were studied. The results showed that f-SWCNTs-KP-ES gel could enhance the skin permeation rate of KP and increase the drug retention of drugs in the skin. The characterization results consistently showed f-SWCNTs is a promising drug carrier. The hybrid nanocarrier prepared by the combination of f-SWCNTs and ethosomes can enhance the transdermal absorption of drugs and improve the bioavailability of drugs, which has a certain significance for the development of advanced hybrid nano-preparations.
Assuntos
Cetoprofeno , Nanotubos de Carbono , Cetoprofeno/química , Cetoprofeno/farmacocinética , Nanotubos de Carbono/química , Administração Cutânea , Pele/metabolismo , Absorção CutâneaRESUMO
Bis-squaramide receptors L1-L4 bearing a dansyl moiety were synthesised and their potential applications as fluorescent probes towards non steroidal anti-inflammatory drugs naproxen and ketoprofen was investigated. A detailed photophysical characterization in CH3CN/DMSO solution (9 : 1 v/v) was conducted and demonstrated that the two macrocyclic receptors L1 and L2 show good sensitivity towards ketoprofen with an ON-OFF fluorescent response, while the two open chain receptors L3 and L4 behave similarly with the three guests considered. DFT theoretical calculations carried out on L2 and L4 as model receptors allowed to propose a possible coordination mode towards the guests. Finally, 1H-NMR spectroscopy in DMSO-d6/0.5% water solution demonstrated that the four receptors interact with the considered guests via H-bonds.
Assuntos
Cetoprofeno , Naproxeno , Naproxeno/farmacologia , Naproxeno/química , Cetoprofeno/farmacologia , Cetoprofeno/química , Dimetil Sulfóxido , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/químicaRESUMO
The mixture of hyoscine N-butyl bromide (HBB) and ketoprofen (KTP) is commonly used for the handling of abdominal spasms and pain relief. There are two challenges that restrict the simultaneous assessment of HBB and KTP in biological fluids and pharmaceuticals. The first issue is the difficulty of elution of HBB and the second one is the presence of KTP as a racemic mixture in all pharmaceutical formulations, which obscures its appearance as a single peak. An ultrasensitive and highly efficient liquid chromatography-mass/mass spectrometric (LC-MS/MS) method is designed and validated for the first concurrent assessment of HBB and KTP in spiked human serum and urine, and pharmaceutical formulations. The estimated linearity ranges for HBB and KTP were respectively, 0.5-500 and 0.05-500 ng/ml, with excellent correlation coefficients. Validation results showed that the value of relative standard deviations were <2% for HBB and KTP. The mean extraction recoveries for HBB and KTP were, respectively, 91.04 and 97.83% in Spasmofen® ampoules; 95.89 and 97.00% in spiked serum; and 97.31 and 95.63% in spiked urine. The presented innovative chromatographic approach was utilized for the measurement of trace amounts of coexisting pharmaceuticals in pharmacokinetics studies and routine therapeutic medication monitoring.
Assuntos
Cetoprofeno , Humanos , Cetoprofeno/química , Brometo de Butilescopolamônio , Escopolamina , Cromatografia Líquida , Espectrometria de Massas em Tandem , Preparações FarmacêuticasRESUMO
Body's homeostasis is dependent on many factors, such as maintaining balance between free radicals formation and degradation. Human serum albumin (HSA) also plays an important role in homeostasis. The aim of this study was thermodynamic analysis of the interaction between ketoprofen (KET), naproxen (NPX), diclofenac (DIC) and HSA, as well as the effect of drug-albumin binding on HSA antioxidant activity using calorimetric and spectrophotometric techniques. Based on the calorimetric analysis it has been shown that accompanied by hydrophobic interaction drugs-albumin binding is an exoenergetic reaction. All analyzed drugs and HSA showed the ability to react with free radicals such as a radical cation, formed as a result of the reaction between 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and potassium persulfate (K2S2O8). Using ABTS assay a synergistic effect of ketoprofen (KET) and naproxen (NPX) on HSA antioxidant activity was observed while the effect of diclofenac (DIC) binding with albumin was probably additive. Because some medications including KET, NPX and DIC belong to over the counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs), it is necessary to understand their influence on HSA antioxidant activity.Communicated by Ramaswamy H. Sarma.
Assuntos
Cetoprofeno , Humanos , Cetoprofeno/química , Naproxeno/farmacologia , Naproxeno/química , Naproxeno/metabolismo , Antioxidantes/farmacologia , Albumina Sérica Humana , Diclofenaco/farmacologia , Diclofenaco/química , Albumina Sérica/química , Anti-Inflamatórios não Esteroides/química , Sítios de LigaçãoRESUMO
Pharmaceutical products such as antibiotics, analgesics, steroids, and non-steroidal anti-inflammatory drugs (NSAIDs) are new emerging pollutants, often present in wastewater, potentially able to contaminate drinking water resources. Adsorption is considered the cheapest and most effective technique for the removal of pollutants from water, and, recently, membranes obtained by wet filtration method of SWCNT aqueous solutions (SWCNT buckypapers, SWCNT BPs) have been proposed as self-standing porous adsorbents. In this paper, the ability of graphene oxide/single-walled carbon nanotube composite membranes (GO-SWCNT BPs) to remove some important NSAIDs, namely Diclofenac, Ketoprofen, and Naproxen, was investigated at different pH conditions (pH 4, 6, and 8), graphene oxide amount (0, 20, 40, 60, and 75 wt.%), and initial NSAIDs concentration (1, 10, and 50 ppm). For the same experimental conditions, the adsorption capacities were found to strongly depend on the graphene oxide content. The best results were obtained for 75 wt.% graphene oxide with an adsorption capacity of 118 ± 2 mg g-1 for Diclofenac, 116 ± 2 mg g-1 for Ketoprofen, and 126 ± 3 mg g-1 for Naproxen at pH 4. Overall, the reported data suggest that GO-SWCNT BPs can represent a promising tool for a cheap and fast removal of NSAIDs from drinking water resources, with easy recovery and reusability features.
Assuntos
Água Potável , Poluentes Ambientais , Cetoprofeno , Diclofenaco/química , Cetoprofeno/química , Naproxeno/química , Anti-Inflamatórios não Esteroides/químicaRESUMO
This work presents a compilation of binding constant (logKass) values in DMSO-d6/H2O (0.5% m/m) for a variety of receptors with 12 carboxylate anions (formate, acetate, lactate, pivalate, sorbate, hexanoate, benzoate, glyphosate, glucuronate, ibuprofen, naproxen, and ketoprofen). A total of 489 logKass values are listed for 100 anion receptor molecules. Most logKass values originate from previously published articles, along with some values for previously unpublished receptor molecules, spanning a workflow of 8 years. The purpose of this study is to serve as a comprehensive information source for selecting suitable receptor candidates to be used in practical carboxylate sensing applications, such as constructing ion-selective electrodes (ISE-s). To support such decision making, all receptors are presented together with lipophilicity (logPo/w) data.
Assuntos
Cetoprofeno , Ânions , Ácidos Carboxílicos , Ibuprofeno/química , Cetoprofeno/química , Naproxeno/químicaRESUMO
Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtained a series of NSAIDs-PIP salts, such as ibuprofen-piperazine (IBU-0.5PIP) salt, indomethacin-piperazine (IND-0.5PIP) salt, sulindac-piperazine (SUL-0.5PIP) salt, phenylbutazone-piperazine (PBZ-0.5PIP) salt, ketoprofen-piperazine (KPF-0.5PIP) salt and flurbiprofen-piperazine (FLB-0.5PIP) salt. The spatial structure, arrangement, interaction and associations were expatiated by single crystal X-ray diffraction. Powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The six new salts had more than 10 folds of solubility and a faster dissolution rate improved corresponding to the bulk drugs in pure water, and the significant improvement of solubility is closely related to the structure of salts.
Assuntos
Flurbiprofeno , Cetoprofeno , Anti-Inflamatórios não Esteroides/química , Varredura Diferencial de Calorimetria , Ibuprofeno/química , Indometacina/química , Cetoprofeno/química , Fenilbutazona , Piperazina , Pós , Sais , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Sulindaco , Água/química , Difração de Raios XRESUMO
Three disposable stochastic sensors based on maltodextrin (dextrose equivalent = 4-7) and nanostructures (copper monolayer, carbon monolayer and carbon-copper composite layer) deposited using cold plasma on copy paper were proposed for the fast analysis of ibuprofen, ketoprofen and flurbiprofen in pharmaceutical formulation samples. The widest linear concentration ranges recorded were: for ibuprofen 1 fmol/L - 1 mmol/L when the disposable stochastic sensor based on carbon monolayer was used, for ketoprofen 1 fmol/L - 1 mmol/L when the disposable stochastic sensors based on copper monolayer and carbon-copper composite layer were used, and for flurbiprofen 1 fmol/L - 10 mmol/L when the disposable stochastic sensor based on carbon-copper composite layer was used. The lowest limit of detection recorded for each non-steroidal anti-inflammatory drug was 1 fmol/L.
Assuntos
Flurbiprofeno , Cetoprofeno , Anti-Inflamatórios não Esteroides , Carbono , Cobre , Composição de Medicamentos , Ibuprofeno/química , Cetoprofeno/químicaRESUMO
Efficiency of drug delivery is product of drug properties and formulation design. Modulating drug's unfavorable properties such as poor solubility or permeation is the first step towards optimum delivery. By combining a drug with a selected bulky counter ion, it can be transformed into a low-melting point salt, i.e., an ionic liquid (IL), with favorable physicochemical properties. In this study, we prepared a novel IL of anti-inflammatory drug, ketoprofen (KP), to enable its transdermal administration. KP was paired with piperine (PI) forming equimolar KP-PI IL, via solvent evaporation. KP-PI IL showed extended stability. Thermal analysis and X-ray diffractometry proved that KP was transformed into a low-melting point amorphous form, while spectroscopic analysis and computational studies demonstrated that KP-PI interaction was mediated by hydrogen bonding. In the IL form, KP's solubility increased due to IL formation by 71 to 83%, while 218% more KP was permeated through rat skin in the IL form, than in a KP/PI mixture. Importantly, upon transdermal administration to rats with induced paw edema; KP-PI IL resulted in a 68% less paw swelling than KP/PI mixture. These findings demonstrate the utility of IL as an economic, simple and efficient strategy for improving the therapeutic application of drugs/drug combinations.