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1.
Talanta ; 207: 120284, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594616

RESUMO

Magnetic carbon nanotubes (CNTs) with encapsulated Co nanoparticles (Co@CNTs), was synthesized by exploiting the one-step pyrolysis strategy using ZIF-67 as template. The as-synthesized Co@CNTs is provided with the nanopores, a large specific surface area, and strong magnetic response. The obtained Co@CNTs was used as magnetic solid-phase extraction adsorbents to extract two profens including flurbiprofen and ketoprofen. The parameters of extraction efficiency, involving extraction time, sample solution volume, ionic strength, pH and the conditions of desorption efficiency, were optimized in detail. After determined by high-performance liquid chromatography-ultraviolet (HPLC-UV), the results evinced that Co@CNTs showed a high extraction efficiency with high enrichment factors of 832 and 672. The good linear range of both flurbiprofen and ketoprofen were all 5.0-1000 ng L-1, with the limit of detection were 0.60 ng L-1 and 0.70 ng L-1, respectively. Furthermore, a valid method for the extraction of flurbiprofen and ketoprofen from human serum was established. The spiking recoveries of two profens were between 86.74% and 97.22%, and the relative standard deviation was less than 6.55%. Co@CNTs can be repeatedly used at least 10 times, indicating its excellent regeneration and reusability. The results demonstrated that the Co@CNTs materials exhibits high enrichment ability and extraction efficiency, playing great promise in MSPE.


Assuntos
Flurbiprofeno/isolamento & purificação , Cetoprofeno/isolamento & purificação , Imãs/química , Nanotubos de Carbono/química , Compostos Organometálicos/química , Extração em Fase Sólida/métodos , Adsorção , Cobalto/química , Flurbiprofeno/sangue , Flurbiprofeno/química , Humanos , Imidazóis/química , Cetoprofeno/sangue , Cetoprofeno/química , Nanopartículas Metálicas/química
2.
Molecules ; 25(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881750

RESUMO

The development of ionic liquids based on active pharmaceutical ingredients (API-ILs) is a possible solution to some of the problems of solid and/or hydrophobic drugs such as low solubility and bioavailability, polymorphism and an alternative route of administration could be suggested as compared to the classical drug. Here, we report for the first time the synthesis and detailed characterization of a series of ILs containing a cation amino acid esters and anion ketoprofen (KETO-ILs). The affinity and the binding mode of the KETO-ILs to bovine serum albumin (BSA) were assessed using fluorescence spectroscopy. All compounds bind in a distance not longer than 6.14 nm to the BSA fluorophores. The estimated binding constants (KA) are in order of 105 L mol-1, which is indicative of strong drug or IL-BSA interactions. With respect to the ketoprofen-BSA system, a stronger affinity of the ILs containing l-LeuOEt, l-ValOBu, and l-ValOEt cation towards BSA is clearly seen. Fourier transformed infrared spectroscopy experiments have shown that all studied compounds induced a rearrangement of the protein molecule upon binding, which is consistent with the suggested static mechanism of BSA fluorescence quenching and formation of complexes between BSA and the drugs. All tested compounds were safe for macrophages.


Assuntos
Líquidos Iônicos/síntese química , Líquidos Iônicos/metabolismo , Cetoprofeno/síntese química , Soroalbumina Bovina/metabolismo , Animais , Bovinos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ésteres/síntese química , Ésteres/química , Transferência Ressonante de Energia de Fluorescência , Líquidos Iônicos/química , Líquidos Iônicos/toxicidade , Cetoprofeno/química , Cetoprofeno/toxicidade , Cinética , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Secundária de Proteína , Células RAW 264.7 , Soroalbumina Bovina/química , Solubilidade , Solventes/química , Água/química
3.
Int J Pharm ; 569: 118634, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31437561

RESUMO

In nanopharmaceutics, a robust manipulation of the preparation process and an accurate prediction of the final product size are very important for developing novel nano drug delivery systems. In the present study, for the first time, a process parameter, i.e. the length of the straight fluid jet, L, is correlated with an experimental parameter, i.e. fluid flow rate, F; a nanofiber property, i.e. diameter, D; and the corresponding drug-sustained release profile. Using a mixed solution consisting of 15% (w/v) polyacrylonitrile and 3% (w/v) ketoprofen in acetone and N,N-dimethylformamide (2:8, v:v) as a spinnable working fluid, a series of medicated nanofibers were prepared under variable F and were characterized. The analysis results disclosed the quantitative relationships among different types of parameters. The process parameter L exhibited a better linear relationship with the nanofibers' diameter (D) than the processing parameter F. These results give a hint that process parameters can be exploited as useful tools for accurately predicting and tailoring the resultant nanofibers' D, and in turn their functional performances. The strategy proposed here presents a new approach to investigate the electrohydrodynamic process and manipulate the functions of nanoproducts through process-property-performance relationships.


Assuntos
Liberação Controlada de Fármacos , Nanofibras/química , Tecnologia Farmacêutica/métodos , Resinas Acrílicas/química , Anti-Inflamatórios não Esteroides/química , Preparações de Ação Retardada/química , Dimetilformamida/química , Cetoprofeno/química
4.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1245-1251, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303597

RESUMO

The aim of the current study was to formulate sustain release (SR) tablets of ketoprofen. Five batches (batch I -V) of matrix based ketoprofen tablet were prepared by dry granulation method using hydroxyl propyl methyl cellulose (15000cps). Compatibility of formulation excipients with drug was explored through FT-IR technique. Various physical and chemical parameters of all tablet batches were evaluated with multi-point dissolution profile (for 24hrs) for formulation optimization. Release kinetics of trials was estimated by model dependent and independent methods. Formulations having excellent quality attributes were then compared with marketed ketoprofen SR tablets. Accelerated stability study was also conducted to compute the shelf life of the optimized formulation. FT-IR scans illustrated the compatibility of ketoprofen with all tablet excipients. On the basis of testing results and controlled release pattern batch II was set to be an optimized trial having shelf life of 37 months. All trial batches (batch I-V) and the marketed brand exhibited highest linearity towards zero order and Korsmeyer-Peppas model with non-fickian anomalous transport (n=0.541-0.655).


Assuntos
Cetoprofeno/química , Cetoprofeno/farmacocinética , Comprimidos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes/química , Derivados da Hipromelose/química , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos/farmacocinética
5.
Int J Mol Sci ; 20(12)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31238499

RESUMO

Cisplatin and several non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to act synergistically or at least additively on several tumor cell lines. Dual-action cisplatin-based Pt(IV) combos containing ketoprofen and naproxen offer good antiproliferative performance on a panel of human tumor cell lines, including a malignant pleural mesothelioma (MPM) one, a very chemoresistant tumor. The main reason of the increased activity relies on the enhanced lipophilicity of these Pt(IV) conjugates that in turn promotes increased cellular accumulation. A quick Pt(IV)→Pt(II) reduction generates the active cisplatin metabolite. The NSAID adjuvant action seems to be almost independent from cyclooxygenase-2 (COX-2) expression in the tumor cells under investigation (lung A-549, colon HT-29, HCT 116, SW480, ovarian A2780, and biphasic MPM MSTO-211H), but it seems to rely (at least in part) on the activation of the NSAID activated gene, NAG-1 (a member of the transforming growth factor beta, TGF-ß, superfamily), which has been suggested to be involved in NSAID antiproliferative activity.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Cetoprofeno/química , Cetoprofeno/farmacologia , Naproxeno/química , Naproxeno/farmacologia , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Pró-Fármacos/química , Pró-Fármacos/farmacologia
6.
Int J Pharm ; 566: 708-716, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31212056

RESUMO

In this study, a facile, economically feasible, and scalable approach to fabricate macroporous poly(vinyl alcohol)-GO (PVA-GO) nanocomposite films with varying filler loadings was demonstrated. The nanocomposite films were prepared using a solvent casting process and employed as a diffusion layer for modulating the transdermal delivery of an anti-inflammatory drug (i.e., ketoprofen). The diffusion membrane was assembled in a three-layer structure with PVA/PVA-GO films between ketoprofen-loaded cellulose and cellulose acetate to mimic skin barrier. Through the incorporation of GO sheets into PVA matrix, the mass diffusion and drug release rate of ketoprofen could be modulated to attain a controlled-release system within period in comparison to that of neat PVA film, which showed more rapid release. It was observed that the dispersion level of GO sheets in the polymer matrix played a crucial role to slow the diffusion rate and drug release, where 3 wt% filler loading gave the slowest rate of release. The results from the present study shed light on the mechanism of and may provide guidelines for modulating drug release rates of NSAID in film-based delivery vehicles for transdermal delivery applications.


Assuntos
Anti-Inflamatórios não Esteroides/química , Grafite/química , Cetoprofeno/química , Nanocompostos/química , Óxidos/química , Álcool de Polivinil/química , Administração Cutânea , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos
7.
Arch Pharm (Weinheim) ; 352(7): e1800339, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31231875

RESUMO

Ketoprofen belongs to one of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione-type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti-inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen-antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic-OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants (IIa-h) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen-antioxidant through the glycolic acid spacer (-CH2 COO; IIIa-h), have also been designed and synthesized. The synthesized codrugs were characterized by IR, 1 H NMR, 13 C NMR, mass spectroscopy and elemental analysis. The in vitro hydrolysis studies showed the lowest hydrolysis (highest stability) in acidic pH 1.2, whereas moderate hydrolysis was seen at pH 7.4 and significant hydrolysis in 80% human blood plasma, as indicated by their t1/2 . The pharmacological evaluation results indicate that these ketoprofen-antioxidant mutual codrugs showed the retention of anti-inflammatory and analgesic activity with a significant reduction in the ulcer index.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Cetoprofeno/farmacologia , Analgésicos/síntese química , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Humanos , Hidrólise , Cetoprofeno/química , Cinética , Estrutura Molecular , Dor/tratamento farmacológico , Picratos/antagonistas & inibidores , Ratos , Úlcera Gástrica/tratamento farmacológico
8.
Ars pharm ; 60(2): 101-108, abr.-jun. 2019. graf, tab, ilus
Artigo em Inglês | IBECS | ID: ibc-186013

RESUMO

Purpose: The purpose of this study was to develop and evaluate nanoemulsion-based gel (nanogel) for transdermal delivery of ketoprofen. Among the various excipients tested, oleic acid, tween 80 and ethanol were selected as oil, surfactant, and co-surfactant respectively. Methods: The nanoemulsions region was identified by constructing pseudo-ternary phase diagrams using aqueous phase titration. The prepared nanoemulsion was subjected to different thermodynamic stability study and the nanoemulsion that passed thermodynamic stability tests were evaluated for viscosity, refractive index, droplet size, transmission electron microscopy, and ex-vivo permeation study using human cadaver skin. Results: On the basis of evaluation C1 formulation, which consists of 3.09 % wt/wt of the oil phase, 60.54 % wt/wt of Smix and 36.36 % wt/wt of distilled water were selected as an optimized formulation and were converted to nanogel using chitosan as a gelling agent. Nanogel was evaluated for ex-vivo and in vivo study. The nanogel showed a significant increase in the anti-inflammatory activity as compared to conventional gel. Conclusion: In conclusion, nanogel could be a promising system to improve transdermal delivery of the ketoprofen


Objetivo: El objetivo de este estudio fue desarrollar y evaluar un gel a base de nanoemulsión (nanogel) para el suministro transdérmico de ketoprofeno. Entre los diversos excipientes probados, se seleccionaron el ácido oleico, la mezcla de 80 y el etanol como aceite, surfactante y co-surfactante. Métodos: La región de las nanoemulsiones se identificó mediante la construcción de diagramas de fase pseudoternarios utilizando la titulación de la fase acuosa. La nanoemulsión preparada se sometió a diferentes estudios de estabilidad termodinámica y la nanoemulsión que pasó las pruebas de estabilidad termodinámica se evaluó para determinar la viscosidad, el índice de refracción, el tamaño de las gotitas, la microscopía electrónica de transmisión y el estudio de permeación ex-vivo utilizando piel de cadáver humano. Resultados: Sobre la base de la evaluación, la formulación de C1, que consiste en 3.09% peso / peso de la fase oleosa, 60.54% peso / peso de Smix y 36.36% peso / peso de agua destilada se seleccionaron como una formulación optimizada y se convirtieron a nanogel utilizando quitosano como Un agente gelificante. Nanogel se evaluó para estudio ex-vivo e in vivo. El nanogel mostró un aumento significativo en la actividad antiinflamatoria en comparación con el gel convencional. Conclusión: En conclusión, el nanogel podría ser un sistema prometedor para mejorar la administración transdérmica del ketoprofeno


Assuntos
Humanos , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Dor/tratamento farmacológico , Géis/administração & dosagem , Géis/química , Emulsões/administração & dosagem , Emulsões/química , Administração Cutânea , Viscosidade , Cadáver , Solubilidade
9.
Int J Pharm ; 566: 173-184, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31132449

RESUMO

The purpose of this work was to compare the particle characteristics and dissolution performance of amorphous solid dispersions (ASDs) of ketoprofen and vinyl-pyrrolidone based polymers prepared using electrospraying and spray drying methods. Solution characteristics (surface tension, viscosity and conductivity) were determined for ethanolic solutions containing different vinyl-pyrrolidone based polymers (PVP and PVPVA) and different ketoprofen to polymer mass ratios. The only statistically significant difference in solution properties between PVP and PVPVA systems was electrical conductivity. The higher conductivity in PVP-containing solutions resulted in smaller, more spherical particles than the equivalent formulations prepared with PVPVA when processed via electrospraying. Electrospraying resulted in powders with higher specific surface area, smaller mean particle size, and narrower particle size distribution relative to the spray-dried material. Amorphisation of ketoprofen via both processes was confirmed using pXRD, DSC and FTIR. Although the specific surface area of the electrosprayed powder was higher than the equivalent spray-dried system, this did not translate into a faster dissolution rate at pH 1.2 but did lead to a faster surface moisture adsorption rate at various relative humidities. The flowability of the powder produced via the electrospraying process is poor compared to the equivalent powder produced via spray drying, which may cause challenges in downstream processing. While the ASD powder produced via electrospraying had a smaller particle size and narrower size distribution compared to equivalent spray-dried ASD, further refinement in terms of a final formulation is needed to translate this benefit into an improved dissolution rate in the case of ketoprofen.


Assuntos
Anti-Inflamatórios não Esteroides/química , Cetoprofeno/química , Povidona/análogos & derivados , Dessecação , Composição de Medicamentos/métodos , Povidona/química
10.
Sci Total Environ ; 678: 173-180, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31075583

RESUMO

Ag-BiOBr-reduced graphene oxide (rGO) was synthesized for the first time and used to promote photocatalytic activity under visible-light irradiation. The Ag-BiOBr-rGO showed an excellent photocatalytic activity to degrade ketoprofen compared with other photocatalysts. The composites were comprehensively characterized to explore the mechanisms of the enhancement. Electron Paramagnetic Resonance and scavenger experiments demonstrated that the superoxide radical was the active species. Ketoprofen was completely removed in 120 min. The high photocatalytic activity and stability of the catalyst indicated that the Ag-BiOBr-rGO may have broad application prospects for eliminating pharmaceuticals from wastewater. Four reaction intermediates of ketoprofen were detected by LC-MS/MS and degradation routes were proposed.


Assuntos
Bismuto/química , Cetoprofeno/química , Modelos Químicos , Poluentes Químicos da Água/química , Catálise , Grafite
11.
Talanta ; 199: 290-295, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30952260

RESUMO

A chitosan membrane composed by 60% (w/w) chitosan and 40% (w/w) Aliquat®336 has been proposed as a new biopolymeric support for electromembrane extraction. The new support has been characterized by Scanning Electron Microscopy, resulting a 30-35 µm thickness. Amoxicillin, nicotinic acid, hippuric acid, salicylic acid, anthranilic acid, ketoprofen, naproxen and ibuprofen have been successfully extracted using the proposed support. Better enrichment factors were obtained for the acidic polar analytes than for the non-steroidal anti-inflammatory compounds (ranging from 118 for hippuric acid and 20 for ibuprofen). Electromembrane extraction was developed applying a DC voltage of 100 V, 1-octanol as supported liquid membrane and 20 min of extraction. The target analytes have also been satisfactorily extracted from human urine samples, providing high extraction efficiencies. The chitosan membrane is presented as a promising alternative for supporting liquid membrane compared to commonly used materials for this purpose.


Assuntos
Biopolímeros/química , Quitosana , Técnicas Eletroquímicas , Amoxicilina/química , Amoxicilina/isolamento & purificação , Hipuratos/química , Hipuratos/isolamento & purificação , Humanos , Ibuprofeno/química , Ibuprofeno/isolamento & purificação , Cetoprofeno/química , Cetoprofeno/isolamento & purificação , Naproxeno/química , Naproxeno/isolamento & purificação , Niacina/química , Niacina/isolamento & purificação , Ácido Salicílico/química , Ácido Salicílico/isolamento & purificação , ortoaminobenzoatos/química , ortoaminobenzoatos/isolamento & purificação
12.
Colloids Surf B Biointerfaces ; 178: 1-7, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30822680

RESUMO

UiO-66 metal-organic framework (MOF) was introduced as ketoprofen delivery system for treating osteoarthritis (OA), and two different kinds of NH2 and NO2 functional groups were grafted into the UiO-66 framework to investigate the effect of functional groups on the drug loading level and release rate. Structural characterization of the samples showed that grafting functional groups had no significant effect on the morphological characteristic and crystal structure of UiO-66. All synthesized MOFs carriers had excellent BET, chemical and thermal stability, though the introduction of NH2 and NO2 functional groups were detrimental for these characteristics. Ketoprofen was successfully loaded on the MOFs carriers, and the results of high performance liquid chromatography (HPLC) indicated UiO-66-NH2 had the highest loading amount (38%). The ketoprofen release experiment manifested that UiO-66-NH2 exhibited lowest release rate and partial release of ketoprofen (about 65%) even after 72 h due to the high hydrogen bonds capacity and alkaline characteristic of -NH2. Furthermore, chondrocyte cytotoxicity experiment manifested that the synthesized MOFs carriers were rather bio-safe, which ensured them to be used as the drug delivery vehicles.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Estruturas Metalorgânicas/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Condrócitos/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Humanos , Ligação de Hidrogênio , Estruturas Metalorgânicas/efeitos adversos , Osteoartrite/tratamento farmacológico
13.
Drug Deliv ; 26(1): 63-69, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30744429

RESUMO

The influence of chiral excipient D-chitosan (CS) on the stereoselective release of racemic ketoprofen (rac-KET) microspheres has been investigated in comparison to those microspheres containing individual enantiomers in vitro and in vivo. Stereoselectivity was observed in vitro release test, with R-KET release slightly higher than that of S-KET, especially in 3% rac-KET loading microspheres. Stereoselectivity is dependent on the content of chiral excipient and pH of release medium. A molecular docking study between CS and KET enantiomers further revealed that S-KET has a stronger interaction with CS compared to R-KET. Moreover, the plasma concentration of KET enantiomers in rats shows substantial differences, as the plasma levels of S-KET were higher than those of R-KET. Plasma levels of enantiomers from the R-KET microspheres had similar stereoselectivity as rac-KET microspheres. The S/R ratio of rac-KET microspheres was significantly lower than that of rac-KET suspension (regular-release formulation) (p<.05), and the differences is 3-5 fold. Besides, rates of R-KET converted to S-KET exhibited differences between rac-KET microspheres and suspension. Similar results were also found between R-KET microspheres and suspension. All investigations suggest that the chitosan interacting preferentially with S-KET to R-KET significantly affect the stereoselective pharmacokinetics of rac-KET from chitosan microspheres in rats.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Quitosana/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Cetoprofeno/administração & dosagem , Microesferas , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Quitosana/química , Quitosana/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Cetoprofeno/química , Cetoprofeno/metabolismo , Masculino , Simulação de Acoplamento Molecular/métodos , Ratos , Ratos Sprague-Dawley , Estereoisomerismo
14.
Chemosphere ; 222: 593-602, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30731379

RESUMO

Nowadays non-steroidal anti-inflammatory drugs (NSAIDs) are often detected in surface water and groundwater. In this study, effects of environmental factors, i.e., solution pH, ionic strength, temperature and surface-bound organic acids, on bonding of three typical NSAIDs (ketoprofen, naproxen and diclofenac) onto goethite were systematically investigated. Column chromatography, batch experiments, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and surface complexation modeling were used to probe the adsorption mechanisms. Bonding of three NSAIDs onto goethite was totally reversible, ionic strength-dependent and endothermic (adsorption enthalpy 2.86-9.75 kJ/mol). These evidences supported H-bonding mechanism, which was further explained by ATR-FTIR observation and a triple planes model. Surface-bound organic acids (phthalic acid, trimellitic acid and pyromellitic acid) by inner-sphere complexation with goethite were hard to be desorbed. Surface-bound phthalic acid increased the uptake of NSAIDs but surface-bound trimellitic acid and pyromellitic acid reduced their adsorption. The reason is that the adsorbed phthalic acid can result in a more hydrophobic surface while adsorbed trimellitic acid and pyromellitic acid increased the surface negative charge and polarity. Finally, adsorption of NSAIDs onto goethite with/without surface-bound organic acids was well described by a free energy model, in which contributions of interactions (e.g., H-bonding and van der Waals) were evaluated.


Assuntos
Ácidos/química , Anti-Inflamatórios não Esteroides/química , Diclofenaco/química , Compostos de Ferro/química , Cetoprofeno/química , Minerais/química , Naproxeno/química , Ácidos/metabolismo , Adsorção , Anti-Inflamatórios não Esteroides/metabolismo , Diclofenaco/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Compostos de Ferro/metabolismo , Cetoprofeno/metabolismo , Minerais/metabolismo , Naproxeno/metabolismo , Concentração Osmolar
15.
Pharm Dev Technol ; 24(8): 947-953, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30676142

RESUMO

Since FDA approval of the first transdermal patch in 1979, the utilizing of skin as a route of systemic drug administration has attracted the attention of the formulation scientists. The liposomes research in the area of transdermal drug delivery has been around for decades. This study aimed at comparing the latest gel-core liposomes (hyaluosomes) with nonconventional liposomal systems such as propylene glycol (PG)-liposomes, ethosomes, transferosomes and conventional liposomes loaded with ketoprofen. The modified thin-film hydration method was used to prepare these liposomal systems; size, zeta potential, EE%, TEM, rheological properties, in vitro release and ex vivo permeation studies were performed. Vesicle size and PDI ranged from 160 nm to 700 nm and 0.15 to 0.5, respectively. More interestingly, thermal gelation and shear-thinning characteristics were only recorded with hyaluosomes; while Newtonian behavior and low viscosity values (2 mPas.s to 6 mPa.s) were shown with all other liposomal systems. Hyaluosomes recorded superior (3-fold increases) transdermal permeation characteristics (flux and permeability coefficient), compared with other liposomal systems. With the advancement in liposomal sciences, this study warrants hyaluosomes as a promising transdermal liposomal system for favorable rheological characteristics as well as superior transdermal permeation that proved greater capacity than conventional and other non-conventional liposomal systems.


Assuntos
Géis/química , Ácido Hialurônico/química , Cetoprofeno/química , Cetoprofeno/metabolismo , Lipossomos/química , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos/métodos , Tamanho da Partícula , Permeabilidade , Propilenoglicol/química , Suínos , Adesivo Transdérmico , Viscosidade/efeitos dos fármacos
16.
AAPS PharmSciTech ; 20(3): 93, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30690657

RESUMO

The objective of the present study is to understand the effects of drug-PEO interactions during the thermal treatment of polyethylene oxide (PEO)-based, directly compressed, abuse-deterrent formulations (ADFs). The drugs studied were dextromethorphan HBr monohydrate, ketoprofen, promethazine HCl, and anhydrous theophylline. Thermal treatment above the melting point of PEO resulted in tablets with higher crushing strength (> 500 N). It was observed that drug-PEO interactions during thermal treatment (80°C) led to solubilization of the incorporated drug. Drugs with higher solubility in the molten PEO, when added at higher weight fractions, interfered with the process of tablet densification which led to an increase in tablet dimensions and created defects in the fused matrix. These changes resulted in the formation of a more porous matrix. Thermal treatment led to a decrease in PEO crystallinity. The decreased crystallinity led to differences in the hydration and dissolution properties of the PEO. The change in dissolution properties of PEO accompanied with the dimensional and microstructural changes resulted in a greater drug release for some of the studied drugs. In conclusion, although thermal treatment above the melting point of PEO is an efficient manufacturing process in imparting crush-resistant features, drug-PEO interactions during the thermal treatment and the impact of thermal treatment on the properties of formulation components may impact tablet properties and lead to potential performance differences.


Assuntos
Preparações de Ação Retardada/química , Dextrometorfano/química , Formas de Dosagem , Cetoprofeno/química , Polietilenoglicóis/química , Prometazina/química , Transtornos Relacionados ao Uso de Substâncias , Comprimidos/química , Teofilina/química , Solubilidade
17.
Biomed Chromatogr ; 33(1): e4370, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30121955

RESUMO

Propranolol, a ß-adrenergic receptor antagonist, is a chiral compound that is marketed as a racemate, but only the (S)-(-)-enantiomer is responsible for the ß-adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers of (RS)-propranolol. In this article a review is presented on different liquid chromatographic methods used for enantioseparation of (RS)-propranolol, using both HPLC and TLC. In addition, some aspects of enantioseparation under achiral phases of liquid chromatography have been briefly mentioned.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Delgada/métodos , Propranolol/química , Propranolol/isolamento & purificação , Cetoprofeno/química , Levofloxacino/química , Propranolol/análise , Estereoisomerismo
19.
Rapid Commun Mass Spectrom ; 33(2): 215-228, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30334294

RESUMO

RATIONALE: In various fields of chemical analyses, structurally unknown analytes are considered. Proper structure confirmation may be challenged by the low amounts of analytes that are available, e.g. in early stage drug development, in metabolism studies, in toxicology or in environmental analyses. In these cases, mass spectrometric techniques are often used to build up structure proposals for these unknowns. Fragmentation reactions in mass spectrometry are known to follow definite pathways that may help to assign structural elements by fragment ion recognition. This work illustrates an investigation of fragmentation reactions for gas chromatography/electron ionization mass spectrometric characterization of benzophenone derivatives using the analgesic drug ketoprofen and seven of its related compounds as model compounds. METHODS: Deuteration and 18 O-labelling experiments along with high-resolution accurate mass and tandem mass spectrometry (MS/MS) were used to further elucidate fragmentation pathways and to substantiate rationales for structure assignments. Low-energy ionization was investigated to increase confidence in the identity of the molecular ion. RESULTS: The high-resolution mass analyses yielded unexpected differences that led to reconsideration of the proposals. Site-specific isotopic labelling helped to directly trace back fragment ions to their respective structural elements. The proposed fragmentation pathways were substantiated by MS/MS experiments. CONCLUSIONS: The described method may offer a perspective to increase the level of confidence in unknown analyses, where reference material is not (yet) available.


Assuntos
Benzofenonas/química , Marcação por Isótopo/métodos , Cetoprofeno/química , Espectrometria de Massas em Tandem/métodos , Éteres/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Estrutura Molecular , Isótopos de Oxigênio
20.
Colloids Surf B Biointerfaces ; 175: 73-83, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30522010

RESUMO

In this paper, chitosan was used as protective agent for dual temperature-/pH-sensitive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate)- based hydrogel nanoparticles (poly(NVCL-co-IA-co-EGDMA)) aiming avoid their undesirable colloidal destabilization at different conditions of body human tissues. Thus, poly(NVCL-co-IA-co-EGDMA) was embedded into chitosan and a new solid dispersion was prepared via spray-drying and ketoprofen was used as carrier. Two different sizes of hydrogel nanoparticles (120.6 nm and 185.9 nm) were evaluated and they exhibited a drug encapsulation efficiency of the 39.6% and 57.8%, respectively. The smaller nanoparticles showed to be faster for releasing of ketoprofen at pH 7.4 and 37 °C due to their larger surface area and higher swelling ability. Chitosan played a role of a secondary barrier for the ketoprofen diffusion, extending its release compared to hydrogel nanoparticles alone. Among two concentrations (40 wt% and 70 wt%) of hydrogel nanoparticles related to chitosan, the first one induced higher percentages of ketoprofen release: 74.2% against 64.6%. In addition, the interactions between chitosan matrix and poly(NVCL-co-IA-co-EGDMA) did not change the multi-responsive behavior of hydrogels, suggesting the chitosan was efficient for keeping integrity of nanoparticles hydrogels. Chitosan/poly(NVCL-co-IA-co-EGDMA) hybrid microparticles seems to be a promising new carrier for release of hydrophobic drugs, such as ketoprofen.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Cetoprofeno/administração & dosagem , Nanopartículas/química , Polímeros/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Caprolactama/análogos & derivados , Caprolactama/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cetoprofeno/química , Cetoprofeno/farmacocinética , Metacrilatos/química , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Polímeros/síntese química , Succinatos/química , Temperatura
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