Utilização dos métodos automáticos em fluxos com detecção espectrofotométrica na determinação de diclofenaco de sódio em formulações farmacêuticas e fluidos corporais / Use of automatic methods in fluxes with spectrophotometric detection in the determination of diclofenac sodium in pharmaceutical formulations and body fluids

RESUMO Este trabalho descreveu e comparou quatro estudos entre si que utilizaram métodos automáticos em fluxo com detecção espectrofotométrica e a reação de oxidação do diclofenaco para determinar diclofenaco em formulações farmacêuticas e fluidos corporais. Para isso, utilizamos os seguintes artigos: Versatility of a multicommuted flow system in the spectrometric determination of three analytes, Sequential injection spectrophotometric method for the assay of anti-inflammatory diclofenac sodium in pharmaceutical preparations, Screening of conditions controlling spectrophotometric sequential injection analysis e Sequential injection spectrophotometric determination of diclofenac in urine and pharmaceutical formulations e detalhamos as metodologias empregadas, os resultados, conclusões obtidas e comparamos entre eles os limites de detecção, desvio padrão relativo e a frequência analítica. Os resultados mostraram diferenças significativas entre métodos empregados e a utilização do Sistema automático do tipo Análise por Injeção Sequencial, apesar deste possuir menor frequência analítica.

SUMMARY This study described and compared four studies that used automatic flow methods with spectrophotometric detection and the oxidation reaction of diclofenac to determine diclofenac in pharmaceutical formulations and body fluids. For this, the following articles were used: Versatility of a multicommuted flow system in the spectrometric determination of three analytes, Sequential injection spectrophotometric method for the assay of anti-inflammatory diclofenac sodium in pharmaceutical preparations, Screening of conditions controlling spectrophotometric sequential injection analysis and Sequential injection spectrophotometric determination of diclofenac in urine and pharmaceutical formulations and we detail the methodologies used, the results, the conclusions obtained and compare the limits of detection, relative standard deviation and analytical frequency. The results showed significant differences between the employed methods and the use of the Automatic System of the Sequential Injection Analysis type, although this one has a lower analytical frequency.

Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial

PURPOSE: To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. METHODS: Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. RESULTS: A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, −0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 (p = 0.530) and the carryover effect was not significant (p = 0.283). CONCLUSIONS: Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.

Evaluación del desempeño de los métodos analíticos aplicados en el diclofenaco sódico 100 mg retard de producción nacional / Evaluation of the performance of the analytical methods applied to Cuban-made 100mg retard sodium diclofenac

Introducción: el diclofenaco sódico es un derivado del ácido fenilácetico y pertenece al grupo de los antinflamatorios no esteroideos con propiedades antinflamatorios, analgésicas y antipiréticas pronunciadas. En la Farmacopea de los Estados Unidos (USP 36, 2013) aparece reportado los métodos analíticos para el control de calidad del diclofenaco sódico en el ingrediente farmacéutico activo y en las tabletas. Objetivos: evaluar el desempeño de los métodos analíticos que se emplean en el control de la calidad de cuantificación y los estudios de estabilidad del ingrediente farmacéutico activo; así como los ensayos de disolución de las tabletas de diclofenaco sódico 100 mg retard de producción nacional. Métodos: en la evaluación del desempeño del método analítico potenciométrico para la cuantificación del ingrediente farmacéutico activo se analizaron los parámetros de linealidad y de precisión (repetibilidad y precisión intermedia). Para el método cromatográfico aplicable a la cuantificación del ingrediente farmacéutico activo en el producto terminado se analizaron los parámetros de especificidad, precisión y exactitud. En el método espectrofotométrico empleado en el ensayo de disolución se tuvo en cuenta la especificidad, la precisión, la linealidad, la influencia del filtrado y la estabilidad de las soluciones analíticas. Resultados: la evaluación del desempeño realizada a los diferentes métodos analíticos, fueron satisfactorias, demostrando que son lineales, precisos y específicos en el rango de concentraciones estudiadas. Conclusiones: se demostró la confiabilidad de los métodos empleados en el control de la calidad y los estudios de estabilidad del ingrediente farmacéutico activo y de las tabletas de diclofenaco sódico 100 mg retard de producción nacional(AU)

Introduction: sodium dicloflenac is a phenylacetic acid derivate included in the non-steroidal anti-inflammatory group, with marked analgesic and antipyretic properties. The US Pharmacopeia (USP 36, 2013) reports the analytical methods for the quality control of sodium diclofenac in the active ingredient and in tablets. Objectives: to evaluate the performance of the analytical methods used in the quality control of quantitation and the stability studies of the active ingredient as well as the dissolution tests of the Cuban-made 100 mg retard sodium diclofenac. Methods: the evaluation of the performance of the potentiometric analytical method for quantitation of the active ingredient analyzed the parameters called linearity and precision (repeatability and intermediate precision). For the chromatographic method applicable to quantitation of the active ingredient in the finished product, parameters such as specificity, precision and accuracy were analyzed. The spectrophotometric method used in the dissolution test took into account specificity, precision, linearity, filtering effect and stability of the analytical solutions. Results: the evaluation of the performance of the different analytical methods was satisfactory and they proved to be linear, precise and specific in the range of studied concentrations. Conclusions: the reliability of the methods for the quality control and of the stability studies of the active ingredient and of Cuban-made 100 mg retard sodium diclofenac was demonstrated(AU)

Controlled Release of Drugs from Cellulosic Wound Bandage Using Silica Microsphere as Drug Encapsulator Module.

Controlled-drug-releasing materials show promising applications in medicinal bandages. In addition, one could incorporate drugs to make such bandages more versatile. During this context, silica microparticles were synthesized, during presence of different drugs namely sodium diclofenac, linoleic acid and recienoleic acid. The morphological characterization shows formation of monodispersed, silica microparticles. FT-IR spectroscopy provided the interaction of the drug molecule at its hydroxide (OH) site with oxygen ions on the silica surface. UV–vis spectroscopy showed persistence of the different drugs signature, especially its R group, confirming its antimicrobial activity even after conjugation. Using zone-of-inhibition studies, the antimicrobial studies were done on two microorganisms, namely, Staphylococcus aureus and Escherichia coli. However, the encapsulator module showed controlled release of all drugs for the duration of 48 h. This work demonstrated an effective protocol to prepare antimicrobial patches for controlled drug delivery.

Evaluation of Prunus domestica gum as a novel tablet binder

To evaluate binding potential of Prunus domestica gum in tablets formulations. Six tablet batches (F-1B to F-6B) were prepared by wet granulation method, containing Avicel pH 101 as diluent, sodium diclofenac as model drug using 10, 15 and 20 mg of Prunus domestica gum as binder and PVP K30 was used as standard binder. Magnesium stearate was used as lubricant. Flow properties of granules like bulk density, tapped density, Carr index, Hausner’s ratio, angle of repose as well as physical parameters of the compressed tablets including hardness, friability, thickness and disintegration time were determined and found to be satisfactory. The FTIR spectroscopic analysis showed that the formulation containing plant gum is compatible with the drug and other excipients used in tablets formulation. Hence the plant gum has role as a potential binder in tablets formulations. The dissolution profile showed that tablets formulations containing Prunus domestica gum 15 mg/200 mg of total weight of tablet as binder showed better results as compared to PVP K30.

Para avaliar a propriedade aglutinante da goma Prunus domestica em formulações de comprimidos, seis lotes (F-1B para F-6B) foram preparados pelo método de granulação úmida, contendo Avicel pH 101 como diluente e diclofenaco de sódio como fármaco modelo, usando 10, 15 e 20 mg de goma de Prunus domestica como agente aglutinante e PVP K30 como aglutinante padrão. O estearato de magnésio foi utilizado como lubrificante. Propriedades de fluxo dos grânulos, como a densidade, índice de Carr, razão de Hausner, ângulo de repouso, bem como parâmetros físicos dos comprimidos, incluindo o tempo de dureza, friabilidade, espessura e desintegração foram determinados e se mostraram satisfatórios. A análise espectroscópica no FTIR mostrou que a formulação contendo goma vegetal é compatível com o fármaco e outros excipientes utilizados na formulação dos comprimidos. Assim, a goma vegetal tem papel potencial como aglutinante em formulações de comprimidos. O perfil de dissolução das formulações que contêm 15 mg/200 mg do peso total do comprimido em goma de Prunus domestica como aglutinante mostrou melhores resultados comparativamente ao PVP K30.

Enteric coating of hard gelatin capsules by the spouted bed process.

The aim of this work was to study the aqueous enteric film coating of hard gelatin capsules in a single step, with no sub coats. A lab scale spouted bed coater with bottom spray feed was employed to coat capsules using gastric resistant methacrylic polymer Eudragit® L30D55. Preliminary experiments were carried out to determine an appropriate coating suspension formulation and to characterize the fluidization behavior of the capsules. Process factor effects, such as the coating time, coating solution viscosity and substrate load on capsule weight gain were studied using a full factorial 23 design. Coating efficiencies ranged from 69.5 to 84.9% and weight gain from 10.8 to 33.2%. The suspension viscosity did not affect significantly the efficiencies. The percentages of gastric resistant capsules increased linearly with weight gains. 100% of the capsules were shown to be gastric-resistant when coated with a minimum of 17% mass increase and their dissolution profiles showed less than 5% drug release after 2 h in HCl solution.

Estudo de formulação de microesferas de acetobutirato de celulose com diferentes concentrações de Poloxamer 188 / Formulation study of cellulose acetate butyrate microspheres withdifferent concentrations of Poloxamer 188

Microesferas de liberação prolongada de diclofenaco de sódio (DFS) foram preparadas empregando o acetobutirato de celulose (ABC) para obtenção da matriz polimérica. Buscando modular a velocidade de liberação do fármaco, a adição de Poloxamer 188 na formulação foi testada, com diferentes proporções de ABC: Pluronic F68 (1:0; 9:1; 3:1 e 1:1). Com exceção da formulação contendo ABC e Pluronic F68 na proporção de 1:1, as outras formulações testadas conduziram à formação de partículas esféricas de tamanho micrométrico. Quando a misturaA BC: Pluronic F68 (1:1) foi empregada, ocorreu à precipitação de uma massa polimérica, sendo este efeito relacionado à elevada concentração do polímero hidrofílico na preparação. Quando comparado com as microesferas preparadas unicamente com ABC, o teor e a eficiência de encapsulação aumentaram com o acréscimo de Poloxamer 188 às formulações. Efeito semelhante foi observado na avaliação da velocidade de liberação do fármaco em meio tampão fosfato pH 7,5. Enquanto as microesferas preparadas apenas com ABC conduziram à liberação de 25% do fármaco encapsulado após 12 horas de ensaio, as microesferas preparadas com relação ABC:Pluronic 9:1 e 3:1 conduziram à liberação de 30% e 70% do fármaco, respectivamente.

Extended-release microspheres containing sodium diclofenac were prepared using the cellulose acetate butyrate (CAB) to obtain the polymer matrix. Looking modulate the rate of drug release, the addition of Poloxamer 188 at different concentrations into formulations was tested in order to obtain CAB to Poloxamer ratio of 1:0, 9:1, 3:1 and 1:1. Excepting for the formulation containing CAB and Poloxamer 1:1, the other formulations resulted in formation of spherical particles of micrometer size range. When the mixture CAB:Poloxamer (1:1) was employed, the precipitation of a polymeric mass occorred, and this effect was related to the high concentration of the hydrophilic polymer in the preparation. When compared to the microspheres prepared only with CAB, the drug content and the encapsulation efficiency increased with the addition of Poloxamer 188 in the formulations. A similar effect was observed in the evaluation of the rate of drug release in pH 7.5 phosphate buffer. While the microspheres prepared with CAB led to release of 25% of the encapsulated drug after 12 hours of testing, the microspheres prepared with CAB: Poloxamer 9:1 and 3:1 resulted in release of 30% and 70% of the drug, respectively.

Effect of cross-linked biodegradable polymers on sustained release of sodium diclofenac-loaded microspheres

The objective of this study was to formulate an oral sustained release delivery system of sodium diclofenac(DS) based on sodium alginate (SA) as a hydrophilic carrier in combination with chitosan (CH) and sodium carboxymethyl cellulose (SCMC) as drug release modifiers to overcome the drug-related adverse effects and to improve bioavailability. Microspheres of DS were prepared using an easy method of ionotropic gelation. The prepared beads were evaluated for mean particle size, entrapment efficiency, swelling capacity, erosion and in-vitro drug release. They were also subjected to various studies such as Fourier Transform Infra-Red Spectroscopy (FTIR) for drug polymer compatibility, Scanning Electron Microscopy for surface morphology, X-ray Powder Diffraction Analysis (XRD) and Differential Scanning Calorimetric Analysis (DSC) to determine the physical state of the drug in the beads. The addition of SCMC during the preparation of polymeric beads resulted in lower drug loading and prolonged release of the DS. The release profile of batches F5 and F6 showed a maximum drug release of 96.97 ± 0.356% after 8 h, in which drug polymer ratio was decreased. The microspheres of sodium diclofenac with the polymers were formulated successfully. Analysis of the release profiles showed that the data corresponds to the diffusion-controlled mechanism as suggested by Higuchi.

O objetivo deste estudo foi elaborar um sistema de entrega de oral de liberação sustentada de diclofenaco sódico (DS) com base em alginato de sódio (SA), como um transportador hidrofílico em combinação com quitosana (CH) e carboximetilcelulose de sódio (SCMC) como modificadores de liberação de fármaco para diminuir os efeitos adversos e melhorar a biodisponibilidade. Prepararam-se microesferas de DS usando um método fácil de geleificação ionotrópica. Avaliaram-se os grânulos preparados quanto ao tamanho médio de partícula, eficiência de compressão, inchaço in vitro, erosão e capacidade de liberação de fármacos. Estes tammbém foram submetidos a vários estudos, como espectrometria no infravermelho com transformada de Fourier (FTIR) para compatibilidade de fármaco e polímero, microscopia eletrônica de varredura para morfologia de superfície, análise de difração de raios-X (XRD) do pós e análise calorimétrica diferencial de varredura (DSC) para determinar o estado físico do fármaco nos grânulos. A adição de SCMC durante a preparação de grânulos do polímero resultou em fármacos com menor carga de fármaco e liberação prolongada do DS. O perfil de liberação dos lotes F5 e F6 apresentou máximo de fármaco liberado de 96,97±0,356% após 8 h após o que a proporção do fármaco no polímero foi diminuída. As microesferas de diclofenaco de sódio com os polímeros foram formuladas com sucesso. A análise dos perfis de liberação mostrou que os dados correspondem ao mecanismo de difusão controlada, como sugerido por Higuchi.

Treatment of mild to moderate Graves' ophthalmopathy with sodium diclofenac: a pilot study / Tratamento da oftalmopatia de Graves leve a moderada com diclofenato de sódio: um estudo piloto

OBJECTIVE: To report the use of sodium diclofenac, an antagonist of PPAR-gamma and cyclooxigenase-2 (COX-2) inhibitor in the treatment of mild to moderate Graves' ophthalmopathy. SUBJECTS AND METHODS: Thirteen patients with clinical activity score (CAS) 2 to 7 were treated during a period ranging from 3 to 12 months (mean 7.8 ± 3.4) with oral sodium diclofenac, 50 mg every 12 hours. RESULTS: Extra-ocular muscle restriction and CAS improved significantly, p = 0.003 and = 0.004, respectively. Ocular pain and diplopia disappeared, except for one patient who reported improvement of these symptoms. No recurrence was found after interruption of treatment. CONCLUSIONS: Treatment of moderate Graves' ophthalmopathy with oral sodium diclofenac is a good, safe and less expensive therapeutic option. Like others new treatment trials, findings must be confirmed in a greater number of patients in a controlled study.

OBJETIVO: Relatar o uso do diclofenato de sódio, um antagonista do PPAR-gama e inibidor da ciclooxigenase-2 (COX-2) no tratamento da leve a moderada oftalmopatia de Graves. SUJEITOS E MÉTODOS: Treze pacientes com CAS (clinical activity score) 2 a 7 foram tratados durante um período de 3 a 12 meses (média 7,6 ± 3,4) com diclofenaco de sódio por via oral na dose de 50 mg a cada 12 horas. RESULTADOS: A restrição da musculatura extraocular e o índice CAS melhoraram de modo significativo, respectivamente p = 0,003 e p = 0,004. A dor ocular e a diplopia desapareceram, com exceção de um paciente que referiu melhora desses sintomas. Não houve recidiva após a interrupção do tratamento. CONCLUSÕES: O tratamento da oftalmopatia de Graves de média gravidade com diclofenaco de sódio por via oral é uma opção boa, segura e de baixo custo. Como outros novos tratamentos, ele deverá ser confirmado em um maior número de pacientes em estudos controlados.

Analgesia multimodal postoperatoria en cirugía ginecológica y obstétrica urgente / Postoperative multimodal analgesia in urgent gynecological and obstetric surgery

Introducción: El dolor luego de una cirugía es frecuente, y en procesos ginecológicos y obstétricos urgentes aparece de manera constante. Objetivo: Evaluar la efectividad de la analgesia multimodal postoperatoria con opioides y anti inflamatorios no esteroideos en cirugía ginecológica y obstétrica urgente. Diseño metodológico: Se realizó un estudio observacional analítico de cohorte prospectivo en 50 pacientes intervenidas de urgencia por ginecología y obstetricia, las cuales se dividieron en un grupo estudio de 25 que recibieron tramadol/diclofenaco y otro de 25 que recibió petidina/duralgina que fueron el control, en el Hospital Militar Central Dr. Luis Díaz Soto entre enero de 2008 y enero de 2010 para evaluar el grado de dolor postoperatorio, la evolución posterior a la cirugía y los efectos adversos asociados. Resultados: La edad promedio fue de 23 años, y el diagnóstico más frecuente fue el embarazo ectópico (21 casos). Aunque tuvieron una analgesia similar en el postoperatorio inmediato (p = 0,061), al transcurrir el tiempo la misma fue mejor combinando Tramadol y Diclofenaco (p = 0,00) que con Petidina y Dipirona. La evolución posterior a la cirugía fue mejor en igual grupo, con movilización más precoz, y mejor cooperación con el equipo de salud, todo ello con escasos efectos adversos. Conclusiones: La mezcla de Tramadol y Diclofenaco sódico ofreció una mejor analgesia posterior al procedimiento quirúrgico en las pacientes estudiadas, constituyendo una alternativa terapéutica a considerar.

Introduction: The pain after surgery is frequent and in urgent gynecological and obstetrics processes it appears in a persistent way. Objective: To assess the effectiveness of postoperative multimodal analgesia using opioids and non-steroid anti-inflammatory drugs in gynecological and obstetric surgery. Methodological design: An analytical and observational of prospective cohort study was conducted in 50 patients operated on due to gynecological and obstetric emergency, which were divided in a study group of 25 tramadol/diclofenac patients and another including 25 pethidine/dipyrone patients as control at the "Luis Díaz Soto" Military Central Hospital between January, 2008 and January, 2010 to assess the postoperative pain level, the course after surgery and the associated adverse effects. Results: The mean age was of 23 years and the more frequent diagnosis was the ectopic pregnancy (21 cases). Although they had a similar analgesia in immediate postoperative period (p= 0,061), in time it was better combined with tramadol/diclofenac (p = 0,00) than with pethydine and dipyrone. The course after surgery was better in a similar group with earlier mobilization and a better cooperation with health staff all this with scarce adverse effects. Conclusions: The combination of tramadol and sodium diclofenac offered a better analgesia after surgical procedure in study patients being a therapeutic alternative to take into account.

Avaliações hematológicas e bioquímicas do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos / Evaluations hematological and biochemical by the use of sodium diclofenac, meloxicam and firocoxib in rats

O presente trabalho avaliou os parâmetros hematológicos e bioquímicos do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos Wistar. Os ratos foram distribuídos em grupos: G1 (controle), G2 (diclofenaco de sódio: 15 mg/kg), G3 (meloxicam: 2,0 mg/ kg), G4 (meloxicam: 10,0 mg/ kg), G5 (firocoxibe: 5,0 mg/ kg) e G6 (firocoxibe: 25,0 mg/ kg). Os fármacos foram administrados por via intragástrica (gavage) a cada 24 horas, durante cinco dias e avaliados em três momentos: M1 (48 horas após o início do tratamento), M2 (96 horas após o início do tratamento) e M3 (72 horas após o término do tratamento). Em cada momento de cada grupo, foram avaliados de cinco a sete animais e realizados os exames laboratoriais. Não foram observadas alterações significativas nos parâmetros bioquímicos e hematológicos com o uso de meloxicam e firocoxibe. O diclofenaco de sódio produziu alterações no eritrograma (redução de hemácias, hematócrito e na taxa de hemoglobina) durante o tratamento e não alterou a contagem das plaquetas e leucometria, com exceção dos basófilos. Não produziu alterações nas atividades de AST, FA, GGT, ureia, creatinina, sódio e potássio. Entretanto, causou diminuições das proteínas plasmática e total sérica, albumina e globulina. Conclui-se que o diclofenaco de sódio não produz grandes alterações no hemograma e exames bioquímicos, enquanto que, o meloxicame o firocoxibe não produzem alterações e efeitos deletérios dose-dependentes nestes exames laboratoriais.

This work has evaluated the hematological and biochemical profile by the use of sodium diclofenac, meloxicam and firocoxib in Wistar rats. The rats were distributed in groups: G1 (control), G2 (diclofenac sodium: 15 mg/kg), G3 (meloxicam: 2.0 mg/ kg), G4 (meloxicam: 10.0 mg/ kg), G5 (firocoxib: 5.0 mg/ kg) e G6 (firocoxib: 25.0 mg/ kg). The drugs were administered intragastrically (gavage) once a day, during five days and evaluated in three moments: M1 (48 hours after the beginning of the treatment), M2 (96 hours after the beginning of the treatment) and M3 (72 hours after the ending of the treatment). In each moment of each group, five to seven animals were evaluated and laboratory exams were performed. There were no significant changes observed in the biochemical and hematological parameters by the use of meloxicam and firocoxib. One of the effects of the sodium diclofenac was eritrogram variation as hematocrit, erythrocytes, hemoglobin decrease during the treatment. In addition, the platelets and total white blood cells counts did not change except for basophil. There was no changes in AST, ALP, GGT, urea, creatinine, sodium, potassium values. However, the values of protein, globulin and albumin decreased. It was concluded that diclofenac sodium does not provide large variations in the hemogram and biochemical profile than the meloxicam and firocoxib do not provide delletery effects in laboratories tests.

Correlação in vitro-in vivo para formas farmacêuticas sólidas de liberação modificada contendo diclofenaco de sódio / In vitro-in vivo correlation for sodium diclofenac modified release tablet formulations

A correlação in vitro-in vivo (CIVIV) refere-se ao estabelecimento de uma relação racional entre as propriedades biológicas, ou parâmetros derivados destas, produzidos por uma forma farmacêutica e suas propriedades ou características físico-químicas. O estabelecimento desse tipo de correlação de dados pode possibilitar a substituição dos estudos in vivo, necessários à demonstração da bioequivalência, pelos estudos in vitro, no caso de alterações no processo de fabricação pós-registro. Os sistemas matriciais apresentam, como principal exemplo de material controlador da liberação, substâncias poliméricas formadoras de matrizes hidrofílicas. Hidroxipropilmetilcelulose (HPMC) é um excipiente de escolha para o preparo de matrizes hidrofílicas, devido à capacidade de formação de gel e controle da liberação. O diclofenaco de sódio (DCL) é um antiinflamatório não esteroidal com ação analgésica e antipirética. Considerando suas características físico-químicas e farmacológicas, é objetivo deste trabalho o estabelecimento de uma CIVIV para DCL incorporado em sistemas matriciais. Os comprimidos de DCL com HPMC foram desenvolvidos e submetidos aos ensaios de dissolução utilizando os aparatos 1, 2, 3 e 4 conforme as especificações farmacopeicas. Foi realizado o estudo de biodisponibilidade, seguindo as normas éticas, com as formulações selecionadas. A partir dos dados de absorção obtidos pela técnica de deconvolução e dos dados de dissolução foi estabelecida a correlação. Os resultados demonstraram que o aumento da concentração de HPMC produziu a redução da velocidade de dissolução e, dependendo da condição de estudo, estas diferenças foram mais ou menos significativas. Os comprimidos com concentração intermediária de HPMC (15 a 20%) foram mais sensíveis às alterações de formulação e das condições do ensaio de dissolução. As formulações contendo 30% de HPMC praticamente não modificaram o perfil de dissolução, mesmo com alterações na formulação e condições de estudo. No...

The term in vitro-in vivo correlation (IVIVC) refers to the establishment of a rational relationship between the biological properties, or a parameter derived from a biological property produced by a dosage form, and a physicochemical characteristic or property of the same dosage form. The establishment of IVIVC enables the substitution of in vivo studies for in vitro studies to evaluate bioequivalence, e.g. in case of post-approval changes. Matrix tablets employ mainly hydrophilic polymers to control drug release. Hydroxypropylmethylcellulose (HPMC) is an excipient of choice for preparation of hydrophilic matrices, due to its gel formation and controlled drug release capacities. Sodium diclofenac (SD) is a non-steroidal anti-inflammatory drug with analgesic and antipyretic effects. Considering its physicochemical and pharmacological characteristics, the objective of this work is to establish an IVIVC for HPMC matrix tablets containing SD. HPMC matrix tablets with SD were formulated and submitted to dissolution testing using apparatus 1, 2, 3 and 4 in accordance with pharmacopoeial specifications. The bioavailability study was carried out under ethical guidelines, using the selected formulations. The correlation was obtained by plotting absorption data, obtained from diclofenac plasmatic curves through a deconvolution technique, against dissolution data. The results showed that the increase of HPMC concentration produces a decrease of the drug dissolution rate and these differences were more or less significant, depending on the study conditions. Tablets with intermediate HPMC concentrations (15 to 20%) were more sensitive to changes in dissolution conditions. Formulations containing 30% HPMC do not present changes in dissolution profiles, even when the formulation or the study conditions change. Formulations F1, F2A, F3 and Voltaren® 50 mg as reference product were used in the bioavailability study to establish IVIVC. The linear correlation between...

Endotoxemia por lipopolissacarídeo de Escherichia coli, em eqüinos: efeitos de antiinflamatórios nas concentrações sérica e peritoneal do fator de necrose tumoral alfa (TNF-alfa) / Escherichia coli lipopolisacharide (LPS) induced endotoxemia in horses: effects of anti-inflammatory drugs on seric and peritoneal tumor necrosis factor alpha (TNF-alpha) concentrations

Avaliou-se a inibição da produção do fator de necrose tumoral alfa (TNF-alfa) devido ao pré-tratamento com antiinflamatório esteroidal (dexametasona) e não esteroidal (diclofenaco sódico) em eqüinos com endotoxemia induzida experimentalmente. Foram utilizados 15 cavalos machos não castrados, distribuídos em três grupos de cinco animais: controle (C), diclofenaco sódico (DS) e dexametasona (DM). A endotoxemia subletal foi induzida pela infusão intravenosa (IV) de 0,1mg/kg/pv de lipopolissacarídeo (LPS) de Escherichia coli 055:B5, administrado em 250ml de solução estéril de cloreto de sódio a 0,9 por cento, durante 15min. Os cavalos do grupo-controle foram tratados com solução de cloreto de sódio a 9 por cento IV. Nos animais do grupo DS, administraram-se, por via oral, 2,2mg/kg de diclofenaco sódico e, nos do grupo DM, 1,1mg/kg de dexametasona IV, respectivamente, 60 e 30min antes da infusão da endotoxina. Mensurou-se, por meio de ensaio de toxicidade com células da linhagem L929, a concentração de TNF-alfa no soro e no líquido peritoneal às 0, 1», 3 e 6 horas após injeção do LPS. No grupo-controle, observou-se aumento significativo de TNF-alfa sérico, em relação ao valor basal e aos grupos DS e DM, 1,15 horas após a indução da endotoxemia. No líquido peritoneal, as concentrações observadas estavam abaixo daquelas da curva padrão de TNF-alfa, não havendo diferença entre os grupos (P>0,05)

The inhibition of tumor necrosis factor alpha (TNF-alpha) production due to pre-treatment with steroidal (dexamethazone) and non-steroidal (sodium diclofenac) anti-inflammatories was studied in horses under experimentally induced endotoxemy. Fifteen stallions were allotted into three groups of five animals each: control (C), sodium diclofenac (SD) and dexamethazone (DM). Sublethal endotoxemy was induced with 0.1mg/kg/bw Escherichia coli 055:B5 lipopolysaccharide (LPS), IV, administrated in 250ml of 0.9 percent sterile sodium chloride, during 15 minutes. Control group horses received 9 percent sodium chloride, IV. SD group animals were orally administrated 2.2mg/kg sodium diclofenac and DM horses received 1.1mg/kg dexamethazone, IV, 30 and 60 minutes before endotoxin infusion, respectively. TNF-alpha concentration was measured in serum and peritoneal fluid by toxicity assay using L929 lineage cells at 0, 1», 3 and 6 hours after LPS injection. Ninety minutes after endotoxemy induction, it was verified a significant increase of serum TNF-a concentration in horses from control group in relation to the basal values as well as results of horses from SD and DM groups. In peritoneal fluid, the measured concentrations were lower than those from TNF-a standard curve and difference among the groups was not verified (P>0.05)

The release of sodium diclofenac from ointments formulated with various excipients

In vitro, the release of sodium diclofenac from different ointment bases at 1% concentration was studied. The rank order of the release pass dialysis membrane was as follow: Emugel carbopol 934, CMC, HPMC gel> emulsified ointment> absorption ointment> hydrophobic ointment.

Investigation on mechanism and drug kinetic release of sodium diclofenac microgranules

The aim of this research is to investigate the mechanism and kinetics of drug release from the core and coated pellets containing sodium diclofenac. Avicel was found to be a good excipient to prepare matrix-type pellets. The drug release could be sustained up to 12 hours. the rate of drug release was fit to Higuchi's model. The microphotograph revealed that the drug release was controlled by the diffusion from the isoluble matrix. The drug release was sustained up to 24 hours. The rate of drug release was fit to Higuchi's model, too. The mechanism of drug release was determined to be the diffusion from insoluble matrix and through the insoluble membrane.

The effect of the bases and added substances on the release and absorption of sodium diclofenac from its different ointment formulations

The effect of the bases and added substances on the release and absorption of sodium diclofenac from its different ointment formulations was studied. The results shown that the released extent of sodium diclofenac from different ointment bases across dialysis membrane was following the order: water soluble bases > emulsion bases > emugel bases > hydrocarbon bases and carbopol 934 gel with 1.2% I-menthol > carbopol 934 gel with 0.5% I-menthol > carbopol 934 gel with 3% oleic acid > carbopol 934 gel only. The percutaneous absorbed extent of sodium diclofenac across the rat hairless skin was evaluated indirectly based on antiinflammatory action on the rat leg stimulated edema by 0.1 ml of 1% caragenin solution. The average reduced percent of leg edema volume of the experimented rat group was obtained in such order: carbopol 934 gel with 1.2% I-menthol > carbopol 934 gel with 0.5% I-menthol > carbopol 934 gel with 3% oleic acid > carbopol 934 gel only. This result demonstrated that there was a correlation between in vitro release and in vivo percutaneous absorption of sodium diclofenac through the rat hairless skin.

Study on determination of relationship between releasing rate in vitro and absorption rate in vivo of sodium diclofenac 100mg tablets LA

The in vitro correlation of sustained release sodium diclofenac 100mg capsule was characterized. Correlation at level A was established between the rate of in vitro release and that of in vivo absorption. Correlation coefficient was found at 0.9705. This correlation coefficient was found at dissolution test used in this research could be applied for quality control of the capsule. The results of the research also showed that the absorption in vivo was suitable for once-a-day dosage form.

Efeito do diclofenaco de sódio na cicatrização da parede abdominal de ratos

The aim of the experiment was to do a valuation of the effect of the sodium diclofenac on the collagenous sinthesis in abdominal wall healing. It was used 40 male Wistar rats to do longitudinal laparotomies with a standardized technique, divided into 2 groups: One without the drug (control group) and another group wich were administrated sodium diclofenac (3mg/kg) every day for 4 days. In the 7th and 14th postoperative day, 10 animals of each group were submitted to euthanasia and the front abdominal wall involving the scar was removed to be prepared to hystological analysis. The segments were prepared with Hematoxilyn-Eosin and Picrosirius Red F3BA, in order to do either a general view of healing process or a quantitative valuation of collagenous. The resultant data were submitted to statistical analysis. It was conclued that the abdominal wall scar in rats treated with sodium diclofenac had less collagenous fibres in the 7th and 14th postoperative days than rats from the control group.

O objetivo deste trabalho foi avaliar o efeito do diclofenaco de sódio na cicatrização da parede abdominal de ratos. Foram utilizados 40 (quarenta) ratos machos Wistar, submetidos a laparotomia com técnica padronizada, distribuidos em dois grupos, um grupo controle e outro onde se administrou o diclofenaco de sódio - 3 mg/kg/dia, via intramuscular durante 4 (quatro) dias consecutivos. Ao sétimo e ao décimo quarto dias de pós operatório, respectivamente, fora realizada a eutanásia, retirando-se a camada músculo-facial abdominal envolvendo a cicatriz operatória para a realização do estudo histológico. Os segmentos foram corados por Hematoxilina-Eosina e Picrosirius Red F3BA, sendo feita observação qualitativa do processo cicatricial e quantitativa do colágeno. Os resultados encontrados foram analisados estatisticamente. Concluiu-se que a cicatriz da parede abdominal de rato tratado com o diclofenaco de sódio apresenta menor quantidade de fibras colágenas no 7 FONT FACE="Symbol">° /font> e 14 FONT FACE="Symbol">° /font> dias de pós-operatório, quando comparado a animal do grupo controle.

A study on the chitosan-tripolyphosphate sodium complex matrix Pellets / 中国海洋药物

VE: Chitosan and sodium tripolyphosphate were used as Complex matrix material for preparing pellets loading sodium diclofenac and its properties were studied. METHODS Chitosantripolyphosphate sodium polyelectrolyte was prepared according to the principle of static electricity polymerization. Its properties and structure characteristics were further investigated. The preparation process, effective factors and the optimal condition for the pellets loading sodium diclofenac were studied. RESULTS IR indicated that the structure of compound contained -NH3+-O-P group. DTA demonstrated that polyelectrolyte had an exothermic peak. There was no interaction between the drug and expedient. SEM showed that the surface of the pellets was regular, dense and the structure of the surface wasn't consistent with the inner. The pellets prepared by this method were uniform, round, well-distributed, hardy, good-mobility and its average diameter was about 10mm. CONCLUSION Chitosan-tripolyphosphate sodium polyelectrolyte could be used as a good matrix material for preparing pellets.