Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros

Medicinas Complementares
Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Curr Drug Metab ; 22(3): 215-223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33334282

RESUMO

BACKGROUND: Pharmacokinetic and pharmacodynamic assessment of ester-containing drugs can be impacted by hydrolysis of the drugs in plasma samples post blood collection. The impact is different in the plasma of different species. OBJECTIVE: This study evaluated the stability of a prodrug, ketoprofen methylester (KME), in commercially purchased and freshly collected plasma of mouse, rat, dog, cat, pig, sheep, cattle and horse. METHODS: KME hydrolysis was determined following its incubation in commercially purchased and freshly collected plasma of those species. Different esterase inhibitors were evaluated for prevention of the hydrolysis in rat, dog and pig plasma. RESULTS: KME was rapidly hydrolyzed in both commercially purchased and freshly collected plasma of mouse, rat, and horse. The hydrolysis was initially quick and then limited in cat plasma. KME hydrolysis was minimum in commercially purchased plasma of dog, pig, sheep and cattle but substantial in freshly collected plasma of those species. Different esterase inhibitors showed different effects on the stability of KME in rat, dog and pig plasma. CONCLUSION: These results indicate that plasma of different species has different hydrolytic activities to estercontaining drugs. The activities in commercially purchased and freshly collected plasma may be different and species-dependent. Esterase inhibitors have different effects on preventing hydrolysis of the ester-containing drugs in the plasma of different species.


Assuntos
Cetoprofeno/análogos & derivados , Animais , Gatos , Bovinos , Química Farmacêutica , Cães , Avaliação Pré-Clínica de Medicamentos/métodos , Estabilidade de Medicamentos , Feminino , Cavalos , Hidrólise , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Cetoprofeno/farmacocinética , Masculino , Camundongos , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Ratos , Ovinos , Especificidade da Espécie , Suínos
2.
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
3.
J Chromatogr A ; 1568: 140-148, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30001901

RESUMO

The quantification of the enantiomeric fraction (EF) during the biodegradation process is essential for environmental risk assessment. In this paper the enantioselective biodegradation of ibuprofen, IBU, and ketoprofen, KET, two of the drugs most consumed, was evaluated. Biodegradation experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant) and supplemented with the racemate of each compound. The inoculum activity was verified using fluoxetine as reference compound. The experimental conditions used (analyte concentration and volume of inoculum) were chosen according to OECD guidelines. In parallel, the optical density at 600 nm was measured to control the biomass growth and to connect it with enantioselectivity. Two RPLC methods for chiral separations of IBU and KET using polysaccharides-based stationary phases were developed. Novel calculations and adapted models, using directly the chromatographic peak areas as dependent variable, were proposed to estimate significant parameters related to the biodegradation process: biodegradation (BD) and EF values at given time, half-life times of (R)- and (S)-enantiomers, number of days to reach a complete BD and the minimum EF expected. The modelled BD and EF curves fitted adequately the data (R2 > 0.94). The use of these new equations provided similar results to those obtained using concentration data. However, the use of chromatographic peak areas data, eliminates the uncertainty associated to the use of the calibration curves. The results obtained in this paper indicate that an enantiorecognition towards IBU enantiomers by the microorganisms present in the activated sludge used in this study occurred, being the biodegradation of (R)-IBU higher than that of (S)-IBU. For KET, non-enantioselective biodegradation was observed.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ibuprofeno/química , Cetoprofeno/química , Esgotos , Biodegradação Ambiental , Calibragem , Ibuprofeno/análise , Cetoprofeno/análise , Cinética , Estereoisomerismo , Águas Residuárias/análise
4.
AAPS PharmSciTech ; 18(5): 1863-1880, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27844417

RESUMO

Various preclinical/clinical studies support the effectiveness of ketoprofen in periodontitis; however, the literature reveals that novel delivery systems have been less explored for the drug in periodontitis. The current investigation aims to explore the potential of a pro-vesicular approach-based proniosomal drug delivery of ketoprofen for its effectiveness and validation in experimental periodontal disease (EPD). Formulations were developed using I-optimal mixture design. Developed formulations were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Selected proniosomal gels were evaluated for mucoadhesiveness, ex vivo drug permeation, and retention studies. Optimized proniosomal gel was evaluated for surface morphology, rheological behavior, texture studies, and pharmacodynamic activity in EPD. The results showed that ketoprofen-loaded proniosomal formulations formed a mucoadhesive hydrogel comprising spherical and flexible vesicles. Viscosity and texture studies showed good adhesion and smoothness, which are desired for enhanced permeation. The disease condition was improved with preserved bone resorption process, that too with intact cementum vis-à-vis marketed gel formulation, when evaluated in the EPD model. The results lead to the conclusion that proniosomes can act as a promising carrier and can be effectively used for improved ketoprofen delivery in periodontal pockets.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Cetoprofeno/administração & dosagem , Periodontite/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Galinhas , Composição de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Liberação Controlada de Fármacos , Cetoprofeno/química , Cetoprofeno/metabolismo , Lipossomos , Masculino , Periodontite/metabolismo , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Ratos , Ratos Wistar , Absorção Cutânea/fisiologia , Suínos
5.
J Pharm Sci ; 105(7): 2146-54, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27287518

RESUMO

This work reports the immobilization of ketoprofen into mesoporous alumina, prepared in different way, to assess their possible applications as a matrix for controlled drug release. The acids' surface properties of the aluminas and their effect on the drug content and release rate were also analyzed. The systems have been characterized by powder X-ray diffractometry, Fourier transformer infrared spectroscopy (FT-IR), N2 adsorption desorption, transmission electron microscopy, and FT-IR of pyridine adsorption. The results show that the drug is incorporated inside the pores of mesoporous alumina, and the content and release rate depend of surface acidity, when increase the surface acidity decrease the drug content and increase the release rate.


Assuntos
Óxido de Alumínio/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Cetoprofeno/administração & dosagem , Ácidos , Adsorção , Anti-Inflamatórios não Esteroides/química , Preparações de Ação Retardada , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Cetoprofeno/química , Microscopia Eletrônica de Transmissão , Porosidade , Piridinas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios X
6.
Drug Deliv ; 23(9): 3294-3306, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27066917

RESUMO

OBJECTIVES: This work aimed at investigating the potential of solid lipid nanoparticles (SLN) as carriers for topical delivery of Ketoprofen (KP); evaluating a novel technique incorporating Artificial Neural Network (ANN) and clustered bootstrap for optimization of KP-loaded SLN (KP-SLN); and demonstrating a longitudinal dose response (LDR) modeling-based approach to compare the activity of topical non-steroidal anti-inflammatory drug formulations. METHODS: KP-SLN was fabricated by a modified emulsion/solvent evaporation method. Box-Behnken design was implemented to study the influence of glycerylpalmitostearate-to-KP ratio, Tween 80, and lecithin concentrations on particle size, entrapment efficiency, and amount of drug permeated through rat skin in 24 hours. Following clustered bootstrap ANN optimization, the optimized KP-SLN was incorporated into an aqueous gel and evaluated for rheology, in vitro release, permeability, skin irritation and in vivo activity using carrageenan-induced rat paw edema model and LDR mathematical model to analyze the time course of anti-inflammatory effect at various application durations. RESULTS: Lipid-to-drug ratio of 7.85 [bootstrap 95%CI: 7.63-8.51], Tween 80 of 1.27% [bootstrap 95%CI: 0.601-2.40%], and Lecithin of 0.263% [bootstrap 95%CI: 0.263-0.328%] were predicted to produce optimal characteristics. Compared with profenid® gel, the optimized KP-SLN gel exhibited slower release, faster permeability, better texture properties, greater efficacy, and similar potency. CONCLUSIONS: SLNs are safe and effective permeation enhancers. ANN coupled with clustered bootstrap is a useful method for finding optimal solutions and estimating uncertainty associated with them. LDR models allow mechanistic understanding of comparative in vivo performances of different topical formulations, and help design efficient dermatological bioequivalence assessment methods.


Assuntos
Cetoprofeno/administração & dosagem , Cetoprofeno/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoimina/administração & dosagem , Polietilenoimina/química , Pele/metabolismo , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/química , Lecitinas/química , Lipídeos/química , Masculino , Nanogéis , Tamanho da Partícula , Permeabilidade , Polissorbatos/química , Ratos , Absorção Cutânea
7.
Chem Biol Drug Des ; 87(6): 878-84, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26715009

RESUMO

This study investigates anti-inflammatory activity with improved pharmacokinetic and non-ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation-induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen. These prodrugs are found to have no gastric ulceration with retained anti-inflammatory activity. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with non-ulcerogenic potential of ester prodrugs of ketoprofen.


Assuntos
Cetoprofeno , Pró-Fármacos , Administração Oral , Animais , Avaliação Pré-Clínica de Medicamentos , Cetoprofeno/efeitos adversos , Cetoprofeno/síntese química , Cetoprofeno/química , Cetoprofeno/farmacocinética , Camundongos , Pró-Fármacos/efeitos adversos , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Ratos , Sigmodontinae , Úlcera Gástrica/sangue , Úlcera Gástrica/induzido quimicamente
8.
Pharm Dev Technol ; 21(2): 204-13, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25431959

RESUMO

Increasing demands for individualized drug treatment has led to an increase in the practice of compounded medications. In this study, we determined the impact of the chemical and physical stability of ketoprofen (10%w/w) cream on its topical/transdermal delivery over a 6-month period. The shelf life of ketoprofen at 25 °C in the pharmaceutical bases LipoDerm and LipoBase (109.94 and 85.9 days) was significantly longer than that in Pluronic Lecithin Organogel (PLO; 44.81 days), justifying extending its beyond use date (BUD) from 30 (USP37/NF32) to at least 60 days in LipoDerm and LipoBase. All the creams evaluated exhibited shear-thinning flow behavior with moderate thixotropy, while the flow properties for LipoBase and PLO creams were altered at storage times greater than 90 days. The percentage of ketoprofen permeated through porcine ear skin was 13.7, 19.1 and 12.7% of the dose from LipoDerm, LipoBase and PLO, respectively and decreased 2- to 3-fold after 28 days of storage. Flux ranging from 85.3 to 446.7 µg/cm(2)/h and topical delivery, on the other hand, were not influenced by storage duration past 28 days. In conclusion, this study justifies extending the BUD of ketoprofen in LipoDerm and LipoBase to 60 days if used for topical delivery only.


Assuntos
Cetoprofeno/administração & dosagem , Cetoprofeno/química , Creme para a Pele/administração & dosagem , Creme para a Pele/química , Pele/metabolismo , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Géis/administração & dosagem , Géis/química , Lecitinas/química , Absorção Cutânea/fisiologia , Suínos
9.
Colloids Surf B Biointerfaces ; 130: 272-7, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25935266

RESUMO

This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 µg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.


Assuntos
Emulsões/química , Glucanos/química , Cetoprofeno/química , Nanopartículas/química , Óleos de Plantas/química , Células 3T3 , Administração Intravenosa , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Glioma/metabolismo , Glioma/patologia , Glioma/prevenção & controle , Hemólise/efeitos dos fármacos , Cetoprofeno/administração & dosagem , Cetoprofeno/farmacocinética , Cinética , Lythraceae/química , Camundongos , Microscopia Eletrônica de Varredura , Estrutura Molecular , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Fotólise/efeitos da radiação , Ratos , Sementes/química , Raios Ultravioleta
10.
Int J Pharm ; 485(1-2): 365-73, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25746948

RESUMO

The goal of this work was to combine the ketoprofen anti-inflammatory effect with the ascorbic acid antioxidant properties for a more efficient treatment of colonic pathologies. With this aim, microspheres (MS) based on both waxy materials (ceresine, Precirol(®) and Compritol(®)) or hydrophilic biopolymers (pectine, alginate and chitosan) loaded with the two drugs were developed, physicochemically characterized and compared in terms of entrapment efficiency, in vitro release profiles, potential toxicity and drug permeation properties across the Caco-2 cell line. Waxy MS revealed an high encapsulation efficiency of ketoprofen but a not detectable entrapment of ascorbic acid, while polymeric MS showed a good entrapment efficiency of both drugs. All MS need a gastro-resistant coating, to avoid any premature release of the drugs. Ketoprofen release rate from polymeric matrices was clearly higher than from the waxy ones. In contrast, the ASC release rate was higher, due to its high hydro-solubility. Cytotoxicity studies revealed the safety of all the formulations. Transport studies showed that the ketoprofen apparent permeability increased, when formulated with the different MS. In conclusion, only polymeric MS enabled an efficient double encapsulation of both the hydrophilic and lipophilic drugs, and, in addition, presented higher drug release rate and stronger enhancer properties.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Colo/metabolismo , Absorção Intestinal , Cetoprofeno/administração & dosagem , Polímeros/química , Ceras/química , Administração Oral , Alginatos/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Ácido Ascórbico/química , Ácido Ascórbico/metabolismo , Células CACO-2 , Química Farmacêutica , Quitosana/química , Diglicerídeos/química , Combinação de Medicamentos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cetoprofeno/química , Cetoprofeno/metabolismo , Cinética , Microesferas , Compostos Orgânicos/química , Pectinas/química , Permeabilidade , Solubilidade , Propriedades de Superfície , Tecnologia Farmacêutica/métodos
11.
Int J Pharm Compd ; 18(4): 348-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25474865

RESUMO

Previous reports indicate that pharmacists are assigning a wide variety of beyond-use dates to extemporaneously compounded medications in topical Pluronic lecithin organogel. The objective of this study was to evaluate the stability of ketoprofen in Pluronic lecithin organogel over a period of six months and to determine an appropriate beyond-use date for this formulation. A stability-indicating high-performance liquid chromatography method for ketoprofen in Pluronic lecithin organogel was validated in our laboratory. Samples of the formulation were analyzed by high-performance liquid chromatography at 0, 7, 14, 21, 28, 45, 60, 90, and 180 days. At each time point, the average concentration and average percent of initial concentration were calculated. The beyond-use date was determined as the time period that the samples were physically stable and maintained at least 90% of the initial concentration. Ketoprofen in Pluronic lecithin organogel was chemically and physically stable for six months when stored at room temperature and protected from light. Therefore, a beyond-use date of six months is appropriate for this preparation.


Assuntos
Anti-Inflamatórios não Esteroides/química , Estabilidade de Medicamentos , Cetoprofeno/química , Cromatografia Líquida de Alta Pressão/métodos , Géis , Lecitinas/química , Poloxâmero/química , Fatores de Tempo
12.
Int J Pharm Compd ; 18(3): 256-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25306775

RESUMO

The present study deals with the preparation and in vitro evaluation of a Pluronic lecithin organogel gel containing ricinoleic acid for transdermal delivery. Blank Pluronic lecithin organogel gels were prepared using ricinoleic acid as the oil phase and characterized for pH, viscosity, gelation temperature, and microscopic structure. The optimized Pluronic lecithin organogel gel formulation was further evaluated using ketoprofen (10%) and dexamethasone (0.5%) as model drugs. The stability and in vitro permeability of ketoprofen and dexamethasone was evaluated and compared with the corresponding control formulation (Pluronic lecithin organogel gel made with isopropyl palmitate as the oil phase). The pH and viscosity of blank Pluronic lecithin organogel gel prepared with ricinoleic acid was comparable with the isopropyl palmitate Pluronic lecithin organogel gel. The thixotropic property of ricinoleic acid Pluronic lecithin organogel gel was found to be better than the control. Drug-loaded Pluronic lecithin organogel gels behaved in a similar manner and all formulations were found to be stable at 25 degrees C, 35 degrees C, and 40 degrees C for up to 35 days. The penetration profile of dexamethasone was similar from both the Pluronic lecithin organogel gels, while the permeability for ketoprofen from Pluronic lecithin organogel gel containing ricinoleic acid was found to be three times higher as compared to the control formulation.


Assuntos
Anti-Inflamatórios/química , Dexametasona/química , Portadores de Fármacos , Excipientes/química , Cetoprofeno/química , Lecitinas/química , Poloxâmero/química , Ácidos Ricinoleicos/química , Administração Cutânea , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Bovinos , Química Farmacêutica , Dexametasona/administração & dosagem , Dexametasona/metabolismo , Composição de Medicamentos , Mucosa Gástrica/metabolismo , Géis , Concentração de Íons de Hidrogênio , Cetoprofeno/administração & dosagem , Cetoprofeno/metabolismo , Permeabilidade , Pele/metabolismo , Absorção Cutânea , Solubilidade , Suínos , Tecnologia Farmacêutica/métodos , Temperatura , Fatores de Tempo , Viscosidade
13.
Drug Dev Ind Pharm ; 39(6): 928-34, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22401710

RESUMO

CONTEXT: Orally disintegrating tablets (ODTs) with sustained release profiles are a new generation of ODTs called orally disintegrating/sustained release tablets (ODSRTs), which are convenient in use and able to slowly release drugs to maintain effective blood concentrations over a prolonged period of time. Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug for ODSRTs. METHODS: We designed a simple two-step process to develop novel ketoprofen orally disintegrating/sustained release tablets (KODSRTs). Firstly, sustained release ketoprofen fine granules were developed by spray drying the aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000. The optimal parameters of spray drying were 100°C for inlet air temperature and 1.5 mL/min for feed rate. Subsequently, the obtained granules were directly compressed into KODSRTs after mixing with lactose, mannitol and a superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP). The characteristics of KODSRTs, especially their potential for extended drug release, were evaluated. RESULTS: Results of an in vitro release test demonstrated that KODSRTs could slowly release ketoprofen for 24 h after disintegrating within 30 s. Extended release properties of KODSRTs were decided by the ketoprofen sustained release fine granules in tablets. Besides, the disintegration time of KODSRTs depended on the percentage of PVPP in tablets. In vivo pharmacokinetic studies in beagles also showed that KODSRTs possessed a significantly extended release profile compared with ketoprofen normal capsules. CONCLUSION: KODSRTs were successfully prepared using a simple two-step process: spray drying and direct compression.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Cães , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Cetoprofeno/metabolismo , Masculino , Comprimidos com Revestimento Entérico
14.
Pak J Pharm Sci ; 25(1): 227-32, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22186334

RESUMO

The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer (Horiba LA300). Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus (PermeGear, USA). Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance (ANOVA). Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Química Farmacêutica/métodos , Cetoprofeno/farmacocinética , Óleos de Plantas/farmacologia , Pele/metabolismo , Adesivo Transdérmico/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Estabilidade de Medicamentos , Géis/administração & dosagem , Géis/efeitos adversos , Géis/química , Cetoprofeno/administração & dosagem , Cetoprofeno/efeitos adversos , Cetoprofeno/química , Tamanho da Partícula , Coelhos , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos
15.
J Pharm Biomed Anal ; 56(2): 221-7, 2011 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-21665404

RESUMO

Thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) techniques were used for assessing the compatibility between ketoprofen (KT) and several excipients as: corn starch, microcrystalline cellulose (PH 101 and PH 102), colloidal silicon dioxide, lactose (monohydrate and anhydre), polyvinylpyrrolidone K30, magnesium stearate and talc, commonly used in the pharmaceutical form. In order to investigate the possible interactions between the components, the thermal curves of KT and each selected excipients were compared with those of their 1:1 (w/w) physical mixtures. For KT, the DSC curves have shown a sharp endothermic peak at 96.8 °C which corresponds to the melting process (literature value: 94-97 °C), respectively the TG curves demonstrated a simple stage of mass loss in the temperature range of 235-400 °C. FT-IR spectroscopy and X-ray powder diffraction (XRPD) were used as complementary techniques to adequately implement and assist in interpretation of the DSC results. On the basis of thermal results, a possible interaction was found between the KT with polyvinylpyrrolidone K30 and magnesium stearate, which could influence the stability of the KT in the binary mixtures. These possible incompatibilities were confirmed by FT-IR and X-ray analysis.


Assuntos
Anti-Inflamatórios não Esteroides/química , Excipientes/química , Cetoprofeno/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cristalografia por Raios X , Formas de Dosagem , Composição de Medicamentos , Estabilidade de Medicamentos , Povidona/química , Difração de Pó , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Esteáricos/química , Tecnologia Farmacêutica/métodos , Temperatura , Termogravimetria
16.
J Oleo Sci ; 60(4): 155-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21427510

RESUMO

Aim of the present work is to study the effects of oil and drug concentrations on droplets size of a nanoemulsion. Newly introduced oil, palm oil esters (POEs) by Universiti Putra Malaysia researchers was selected for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Nanoemulsions were prepared with different concentrations of oil and drug and their effects on droplets size were studied by laser scattering spectroscopy (Nanophox). The results of droplets size analysis shows the droplets size increase with increasing concentration of oil and drug concentrations. It can be concluded from this study, that oil and drug concentrations have an effect on the droplets size of POEs nanoemulsion system.


Assuntos
Ésteres , Cetoprofeno/administração & dosagem , Nanopartículas , Óleos de Plantas , Química Farmacêutica , Emulsões , Ésteres/administração & dosagem , Cetoprofeno/química , Óleo de Palmeira , Tamanho da Partícula , Óleos de Plantas/administração & dosagem
17.
J Oleo Sci ; 59(12): 667-71, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21099145

RESUMO

Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Edema/tratamento farmacológico , Ésteres/química , Cetoprofeno/farmacologia , Nanoestruturas/química , Óleos de Plantas/química , Analgésicos/síntese química , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Carragenina , Edema/induzido quimicamente , Emulsões/síntese química , Emulsões/química , Emulsões/farmacologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Cetoprofeno/análogos & derivados , Cetoprofeno/química , Masculino , Dor/induzido quimicamente , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
18.
Zhongguo Zhong Yao Za Zhi ; 35(15): 1943-6, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-20931842

RESUMO

OBJECTIVE: To study the stability and degradation kinetics of Ketoprofen-Paeonol conjugate (Ket-Pae). METHOD: RP-HPLC method was used to determine the solubility and partition coefficient of Ket-Pae. Stability test was carried out to investigate the factors affecting Ket-Pae. The kinetic studies of Ket-Pae degradation were conducted in different pH buffer solutions and 80% rat plasma at 37 degrees C. RESULT: Ket-Pae showed significant degradation phenomenon at high temperature. The solubility of Ket-Pae was decreased about 200 to 300 times compared with parent drugs in water while the lnP increased about 4 times. The degradation curve displayed a V-shape, and kept maximum stability at week acidic (pH 5.0, t(1/2) = 11.4 d). Ket-Pae degraded quickly with very short half life of 1.3 min in plasma, therefore easily released ketoprofen and paeonol. CONCLUSION: The lipophilicity of Ket-Pae is increased, its stability is affected by temperature and pH value.


Assuntos
Acetofenonas/química , Medicamentos de Ervas Chinesas/química , Cetoprofeno/química , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Cinética , Solubilidade
19.
Polim Med ; 39(3): 9-15, 2009.
Artigo em Polonês | MEDLINE | ID: mdl-19873929

RESUMO

An attempt was made to use dry standardized extract from Harpagophytum procumbens of confirmed anti-inflammatory activity in formulations applied on skin. To obtain synergy in the area of analgesic and anti-inflammatory activity formulations were produced containing plant extract and nonsteroidal anti-inflammatory drug (ketoprofen). All the preparations were prepared on the base of acrylic acid polymers (Carbopol Ultrez 10, Carbopol 980). The formulations were subjected to complementary physicochemical investigations. Viscosity parameters (structural viscosity, yield stress, thixotrophy) were determined with cone-plate digital rheometer. Potentiometric method was used to measure pH of the produced hydrogels. The test for ketoprofen pharmaceutical availability through a semipermeable membrane to acceptor fluid was performed in vitro. The rate of the process of release was tested by determining the quantity of the therapeutic agent diffusing into acceptor fluid at defined time intervals by spectrophotometric method. The effect of Harpagophytum procumbens extract components on ketoprofen diffusion was estimated. Viscosity tests revealed that all the formulations are viscoelastic systems having yield stress. All model formulations were tested 24h after production and after 6-month storage. All the formulations demonstrate rheological stability and high pharmaceutical availability of ketoprofen. The suggested formulations can be an alternative for market preparations applied on skin of anti-inflammatory and analgesic activity.


Assuntos
Anti-Inflamatórios/química , Harpagophytum/química , Cetoprofeno/química , Fitoterapia , Extratos Vegetais/química , Preparações de Plantas/química , Acrilatos/química , Administração Tópica , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Química Farmacêutica , Difusão , Sinergismo Farmacológico , Elasticidade , Hidrogéis/química , Concentração de Íons de Hidrogênio , Cetoprofeno/administração & dosagem , Modelos Biológicos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Preparações de Plantas/administração & dosagem , Preparações de Plantas/farmacocinética , Reologia , Viscosidade
20.
Polim Med ; 39(3): 17-26, 2009.
Artigo em Polonês | MEDLINE | ID: mdl-19873930

RESUMO

Medications originating from plants can be successfully applied in the treatment of rheumatic pain beside those from the nonsteroidal anti-inflammatory drugs (NSAIDs). An attempt was made to produce a new form of a drug applied on skim, which contains NSAID and glycol plant extract in its composition. The aim of the study was to obtain synergy in the area of analgesic and antiinflammatory activity. Formulations containing NSAID (ketoprofen) and formulations containing glycol plant extracts of confirmed anti-inflammatory and analgesic activity (extract from sage, extract form arnica) were produced on the basis of acrylic acid polymers (Carbopol Ultrez 10, Carbopol 980). Moreover, formulations were also produced containing ketoprofen and glycol plant extract in their composition. Viscosity parameters of the tested formulations (structural viscosity, yield stress, thixotrophy)were determined with cone-plate digital rheometer. Potentiometric method was used to measure pH of the produced hydrogels. The test for therapeutic agents pharmaceutical availability was performed with membrane method. Spectrophotometric method was used to estimate the quantity of the released therapeutic agent. The usefulness of acrylic acid polymers (Carbopol Ultrez 10, Carbopol 980) was assessed for the application in the prescription of dermatological hydrogels as well as their compatibility with ketoprofen and active substances contained in glycol plant extracts. Pharmaceutical availability was tested of ketoprofen and therapeutic agents contained in the investigated plant extracts. Furthermore, the effect of the components of extracts on the process of ketoprofen release to acceptor fluid through a semipermeable membrane was estimated.


Assuntos
Arnica , Hidrogéis/química , Cetoprofeno/química , Extratos Vegetais/química , Salvia officinalis , Acrilatos/química , Resinas Acrílicas/química , Administração Cutânea , Anti-Inflamatórios/química , Química Farmacêutica , Composição de Medicamentos , Sinergismo Farmacológico , Concentração de Íons de Hidrogênio , Fitoterapia , Viscosidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA