Starch-based orodispersible film for diclofenac release

Abstract The form of drug administration affects the success of treatment, since it can influence adherence of the patient to the therapy. The use of orodispersible films has emerged as a way to overcome some drawbacks of conventional methods of drug delivery, especially for patients experiencing difficulty in swallowing. These films are prepared using a matrix that incorporates the drug and contains other substances that confer the properties of the system. The present work describes the use of thermoplastic starch as a carrier for the model drug diclofenac, including film preparation and testing of its orodispersible potential. Preparation of the film employed a microwave oven to gelatinize and plasticize corn starch, with incorporation of the model drug, followed by solvent-casting. The samples were characterized using mechanical tests, analyses of water uptake and water content, and Fourier transform infrared spectroscopy. The results indicated that the film presented promising properties as an alternative system for oral drug administration, with good incorporation and distribution of the drug in the matrix. The material displayed satisfactory mechanical properties, which are crucial for this type of material, due to the need for oral administration and handling before use.

Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles

Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

A comparative study of two separate analytical techniques for the simultaneous determination of diclofenac sodium and diacerein from combined dosage form

ABSTRACT Diclofenac sodium (DS) and diacerein (DC) have emerged as a potential combination therapy for the treatment of knee osteoarthritis. Therefore a validated analytical method is essential for the simultaneous estimation of both from combined dosage form. A ratio derivative spectrophotometric and a chromatographic technique have been developed for the simultaneous determination of DS and DC. The quantification was done at 263.00 nm for DC and 304.50 nm for DS in the first method, whereas 257 nm for DC and at 274 nm for DS for LC-DAD analysis in chromatographic method using acetate buffer and methanol as the mobile phase at a flow-rate 0.50 mL/min. Both of these methods are found to be linear in the concentration range under study with r2 value 0.999 and 0.996 for DS and DC respectively in ratio derivative spectroscopy and 0.998 and 0.999 for DS and DC respectively in LC-DAD study. Both of these methods are found to be accurate and precise, though greater robustness and precision is observed with chromatographic analysis over the ratio derivative spectroscopy. Statistically there was no significant difference between proposed ratio derivative spectrophotometric and LC-DAD methods.

Differential pulse voltammetric determination of diclofenac in pharmaceutical preparations and human serum / Pulso diferencial determinação voltamétrica de diclofenaco em preparações farmacêuticas e em soro humano

This article describes a differential pulse voltammetric (DPV) method for the determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electro-oxidation of diclofenac at platinum electrode in 0.1 M TBAClO₄/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL^-1and 2-20 μg mL^-1 in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.87, and accuracy (relative error) was better than 4.12%. The method developed in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. In addition, the proposed technique was successfully applied to spiked human serum samples. No electro-active interferences from the endogenous substances were found in human serum...

Este artigo descreve um método de voltametria de pulso diferencial (VPD) para a determinação de diclofenaco em preparações farmacêuticas e em soro humano. O método proposto foi baseado em eletroxidação de diclofenaco no eléctrodo de platina em solução 0,1 M TBAClO₄/acetonitrila. Dois picos de oxidação bem definidos foram observados em 0,87 e 1,27 V, respectivamente. As curvas de calibração obtidas utilizando-se valores de corrente medidos por segundo pico foram lineares no intervalo de concentração de 1,5-17,5 μg mL^-1e 2-20 μg mL^-1em eletrólito suporte e soro, respectivamente. Precisão e exatidão também foram verificadas em todos os meios. Valores de precisão intra- e inter-dia para o diclofenaco foram inferiores a 3.87 e a precisão (erro relativo) foi melhor do que 4,12%. O método desenvolvido neste estudo é exato, preciso e pode ser facilmente aplicado a Diclomec, Dicloflam e comprimidos Voltaren, como preparação farmacêutica. Além disso, a técnica proposta foi aplicada com sucesso em amostras de soro humano. Não se observaram interferências das substâncias endógenas no soro humano...

Estandarización de un método por HPLC para cuantificar diclofenaco en muestras de microdiálisis mediante fotoderivatización precolumna / Standardization of a HPLC method for quantitation of diclofenac in microdialysis samples through precolumn photoderivatization

Introducción: la cuantificación del diclofenaco en muestras de pequeño volumen y baja concentración de analito es compleja y requiere de un método analítico sencillo, altamente sensible y reproducible. Objetivo: estandarizar un método por cromatografía líquida de alta resolución (HPLC) con fotoderivatización precolumna, para cuantificar diclofenaco en muestras de pequeño volumen y baja concentración de analito. Métodos: se obtuvieron los fotoproductos del diclofenaco mediante irradiación de muestras a l= 254 nm en celdas de cuarzo, politetrafluoroetileno (PTFE) y polivinilcloruro (PVC), colocadas en diferentes posiciones del área de irradiación durante 6, 24 y 60 min respectivamente. Para la separación de los fotoproductos se utilizó una columna C-18 Agilent Eclipse Plus (5 µm; 150 mm; 4,6 µm id.), usando como fase móvil acetonitrilo (ACN): agua, acidulada con ácido fosfórico hasta pH= 3,0 en diferentes proporciones hasta encontrar la óptima; la temperatura empleada fue de 30 °C, el flujo de 1 mL/min y el volumen de inyección de 20 µL. Se detectaron los fotoproductos por fluorescencia a lambas de excitación y emisión de 286 y 360 nm respectivamente. Resultados: la fotodegradación del diclofenaco en celdas de PTFE ocurrió en 6 min cuando se irradiaron soluciones a 254 nm en el centro del área de irradiación. La separación de los tres fotoproductos principales se logró utilizando una fase móvil ACN: agua, acidulada con ácido fosfórico hasta pH= 3,0; 65:35. El fotoproducto que eluye a 3,4 min se produjo en concentraciones altas y estables las cuales presentaron una tendencia lineal en un gráfico de respuesta del equipo (área) vs. concentración de diclofenaco en un rango entre 1,25-500 ng/mL. Conclusiones: se logró estandarizar un método por HPLC para la cuantificación de diclofenaco presente en muestras de pequeño volumen y baja concentración, el cual podrá someterse a proceso de validación(AU)

Introduction: the diclofenac quantitation in small volume and low analyte concentration samples is complex and requires a simple, highly sensitive and reproducible analytical method. Objective: to standardize a high performance liquid chromatography with precolumn photoderivatization to quantitate diclofenac in small volume and low analyte concentration samples. Methods: diclofenac photoproducts were obtained by irradiating samples at l= 254 nm in quartz polytetrafluoroethylene (PTFE) and polyvinyl chloride (PVC) cells placed in different positions of the irradiation area for 6, 24 and 60 minutes respectively. For the separation of photoproducts, a C-18 Agilent Eclipse Plus column (5 µm, 150 mm; 4.6 µm id.) was used, with a mobile phase containing a mixture of acetonitrile and water pH 3.0 adjusted with ortho-phosphoric acid, in different proportions until the optimal one was found; the flow rate of mobile phase was 1.0 mL/min with column temperature of 30 °C. The sample injection volume was 20 µL. Photoproducts were detected through fluorescence with excitation and emission wavelength at 286 and 360 nm respectively. Results: diclofenac photodegradation in PTFE cells occurs within 6 minutes when solutions are irradiated at 254 nm in the central part of the irradiation area. The separation of the three major photoproducts was accomplished using a mobile phase of acetonitrile: water adjusted with ortho-phosphoric up to pH= 3.0;65:35. The photoproduct at 3.4 minutes was eluted at high stable concentrations, with a linear trend presented in an area graph versus diclofenac concentration in the range of 1.25-500 ng/mL. Conclusions: a new HPLC-method for quantitation of diclofenac in small volume and low concentration samples was standardized; it may undergo validation process(AU)

Confirmación de dexametasona y diclofenaco por LC-MS-MS como adulterantes en un producto herbolario / Dexamethasone and diclofenac by LC-MS-MS as herbal product adulterants

Objetivo. Confirmar la presencia de dexametasona y diclofenaco como adulterantes de un producto comercializado como de origen natural. Material y métodos. Para la identificación y confirmación de la presencia de los fármacos se utilizó un método de análisis instrumental por cromatografía de líquidos de alta presión acoplado a espectrometría de masas en tándem. Resultados. En el análisis de 11 frascos de Reumofan Plus obtenidos de pacientes y médicos de la localidad se confirmó la presencia de dexametasona y diclofenaco. La metodología utilizada permitió separar los esteroisómeros dexametasona y betametasona, las abundancias relativas de iones productos 237.2 y 279.2 m/z permiten diferenciar espectralmente un compuesto de otro. Conclusiones. Se confirmó la presencia de dexametasona y diclofenaco en muestras de un producto comercializado como "100% natural" obtenidas de diferentes pacientes o médicos en el periodo enero a diciembre de 2011.

Objective. To confirm the presence of dexamethasone and diclofenac as adulterants of an herbal product. Materials and methods. For identificaction and confirmation of drugs a method of instrumental analysis by liquid chromatography coupled with high pressure tandem mass spectrometry was used. Results. The presence of dexamethasone and diclofenac was confirmed in samples of 11 bottles of Reumofan Plus obtained from patients and/or physicians. The methodology used, allowed separation of stereoisomers dexamethasone and betamethasone, the relative abundances of product ions 237.2 and 279.2 m / z spectrally differentiate the compounds. Conclusions. The presence of dexamethasone and diclofenac was confirmed in samples of a product marketed as "100% natural" obtained from patients and / or physicians in a period from January to December, 2011.

In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.

Para exercer ação farmacológica, medicamentos tópicos de aplicação cutânea precisam, primeiramente, liberar o fármaco do veículo, para que desta forma ele se torne disponível para penetração nas camadas da pele, até atingir seu local de ação. A liberação do fármaco do veículo depende principalmente das características da formulação. Até a presente data, para registrar um medicamento genérico ou similar no Brasil não se exigem testes de desempenho para produtos tópicos de ação local. O presente trabalho teve como objetivo avaliar a liberação in vitro de especialidades farmacêuticas de diclofenaco dietilamônio gel do mercado farmacêutico brasileiro, usando o sistema de célula de difusão vertical. Avaliaram-se fatores que influenciam o teste como o tipo de membrana usada nos ensaios de liberação e características da formulação que impactam a velocidade de difusão. A legislação vigente no País permite que medicamentos genéricos contenham excipientes diferentes do medicamento referência. Esta diferença afetou a liberação do fármaco do veículo. Dos quatro medicamentos genéricos testados apenas um seria considerado equivalente ao medicamento referência Cataflam Emulgel®. As membranas de acetato de celulose e polietersulfona testadas apresentaram-se intercambiáveis nos estudos de liberação desse produto.

A simple method for the quantification of diclofenac potassium in oral suspension by high-performance liquid chromatography with UV-detection

A rapid, simple and low cost method was developed to determine diclofenac potassium (DP) in oral suspension, using a reverse-phase column (C8, 150 mm x 4.6 mm, 5 µm), mobile phase containing methanol/buffer phosphate (70:30 v/v, pH 2.5), at a flow rate of 1.0 mL/min, isocratic method, and ultraviolet detection at 275 nm. A linear response (r = 1.0000) was observed in the range of 10.0-50.0 µg/mL. Validation parameters such as linearity, specificity, precision, accuracy and robustness were evaluated. The method presented precision (repeatability: relative standard deviation = 1.21% and intermediate precision: between-analyst = 0.85%). The specificity of the assay was evaluated by exposure of diclofenac potassium under conditions of stress such as hydrolysis, photolysis, oxidation and high temperature. The method presented accuracy values between 98.28% and 101.95%. The results demonstrate the validity of the proposed method that allows determination of diclofenac potassium in oral suspension and may be used as an alternative method for routine analysis of this product in quality control.

Desenvolveu-se método simples, de baixo custo para determinar o diclofenaco potássico (DP) em suspensão oral, usando coluna de fase reversa (C8, 150 mm x 4,6 mm, 5 µm), fase móvel contendo metanol/tampão fosfato (70:30 v/v, pH 2,5), com fluxo de 1,0 mL/min, método isocrático e detecção no ultravioleta a 275 nm. Observou-se resposta linear (r = 1,0000) na faixa de 10,0-50,0 µg/mL. Avaliaram-se parâmetros de validação, como linearidade, especificidade, precisão, exatidão e robustez. O método apresentou precisão (repetibilidade: desvio padrão relativo = 1,21% e precisão intermediária: entre analista = 0,85%). A especificidade do ensaio foi avaliada pela exposição do diclofenaco potássico a condições de estresse, tais como hidrólise, fotólise, oxidação e alta temperatura. O método apresentou valores de exatidão entre 98,28% e 101,95%. Os resultados mostram a validade do método proposto, que permite a determinação de diclofenaco potássico em suspensão oral e pode ser utilizado como alternativa para análise de rotina desse produto no controle de qualidade.

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.

Development and evaluation of a hot-melt coating technique for enteric coating

Conventional enteric coating requires the use of organic based polymers which are equally hazardous to the environment and operating personnel. Hot-melt coating avoids the use of solvents and is a safer and time-saving process. The present study was designed to assess the efficacy of hot-melt coating (HMC) as an enteric coating technique. Pellets prepared by extrusion spheronization were selected as the core formulation for a model of the gastric irritant drug diclofenac sodium (DFS) because of their innate advantages over single-unit formulations. Stearic acid (SA) and palmitic acid (PA) were evaluated as enteric hot-melt coating materials. HMC was carried out in a specially modified coating pan by applying SA and PA in molten state onto preheated pellets to achieve a coating level of 5-15 %w/w. Hot-melt coated pellets were evaluated for disintegration pH and in vitro dissolution in the pH range 1.2 to 6.8, along with basic micromeritics. SEM of coated pellets showed a uniform and smooth coating. These results indicated that HMC of both SA and PA exhibited very good enteric coating ability. The coated pellets showed negligible drug release in acidic pH. As the pellets were subsequently transferred to a higher pH level, a gradual increase in release of the drug from the pellets was observed with increasing pH of the dissolution media. The release was dependent upon coating extent, providing sustained enteric release as opposed to abrupt release with mixed release kinetics.

O revestimento entérico convencional requer o uso de polímeros orgânicos os quais são igualmente danosos ao meio ambiente e ao pessoal que o executa. O revestimento por fusão a quente evita o uso de solventes e é processo mais seguro e que consome menos tempo. O presente estudo foi planejado para avaliar a eficácia do revestimento por fusão a quente (RFQ) como técnica de revestimento entérico. Os péletes preparados por esferonização por extrusão foram selecionados como formulação central para modelo de fármaco irritante gástrico, o diclofenaco sódico (DFS) em razão das vantagens inerentes sobre as formulações de única dose. O ácido esteárico (AE) e o ácido palmítico (AP) foram avaliados como materiais para o revestimento de fusão a quente. O RFQ foi realizado em recipiente especialmente modificado, aplicando AS e PA no estado fundido em péletes pré-aquecidos para atingir nível de revestimento de 5 a 15% p/P. Os péletes revestidos por fusão a quente for avaliados quanto ao pH de desintegração e à dissolução in vitro na faixa de pH de 1,2 a 6,8, juntamente com base micromerítica. O SEM dos péletes revestido mostrou revestimento uniforme e plano. Esses resultados indicaram que o RFQ tanto do AE quanto do AP apresentou capacidade de revestimento muito boa. Os péletes revestidos mostraram pouca liberação do fármaco em pH baixo. Como os péletes foram, subsequentemente, transferidos para pH mais altos, observou-se aumento gradual na liberação do fármaco dos péletes com o aumento do pH do meio de dissolução. A liberação foi dependente da extensão do revestimento, sendo a liberação entérica controlada, contrariamente à liberação abrupta com cinéticas mistas.

Influence of binder type and process parameters on the compression properties and microbial survival in diclofenac tablet formulations

The influence of binder type and process parameters on the compression properties and microbial survival in diclofenac tablet formulations were studied using a novel gum from Albizia zygia. Tablets were produced from diclofenac formulations containing corn starch, lactose and dicalcium phosphate. Formulations were analyzed using the Heckel and Kawakita plots. Determination of microbial viability in the formulations was done on the compressed tablets of both contaminated and uncontaminated tablets prepared from formulations. Direct compression imparted a higher plasticity on the materials than the wet granulation method. Tablets produced by wet granulation presented with a higher crushing strength than those produced by the direct compression method. Significantly higher microbial survival (p< 0.05) was obtained in formulations prepared by direct compression. The percent survival of Bacillus subtilis spores decreased with increase in binder concentration. The study showed that Albizia gum is capable of imparting higher plasticity on materials and exhibited a higher reduction of microbial contaminant in the formulations. The direct compression method produced tablets of reduced viability of microbial contaminant.

A influência do tipo de ligante e os parâmetros do processo de propriedades de compressão e sobrevivência microbiana em comprimidos de diclofenaco foram estudados utilizando uma nova goma de Albizia zygia. Os comprimidos foram produzidos a partir de formulações de diclofenaco contendo amido de milho, lactose e fosfato bicálcico. As formulações foram analisadas usando os gráficos de Heckel e Kawakita. A determinação da viabilidade microbiana nas formulações foi feita nos comprimidos contaminados e não contaminados preparados a partir de formulações. A compressão direta confere maior plasticidade dos materiais do que o método de granulação úmida. Comprimidos produzidos por granulação úmida apresentaram maior força de esmagamento do que aqueles produzidos pelo método de compressão direta. Observou-se sobrevivência significativamente maior (p<0,05) em formulações preparadas por compressão direta. A sobrevivência percentual dos esporos de Bacillus subtilis diminuiu com o aumento da concentração do agregante. O estudo mostrou que a goma de Albizia é capaz de conferir maior plasticidade aos materiais e apresentou maior redução da contaminação microbiana nas formulações. O método de compressão direta produziu comprimidos com viabilidade reduzida de contaminantes microbianos.

Determinación de diclofenaco de sodio por cromatografía líquida de alta resolución en un colirio al 0, 1 por ciento / Determination of Diclofenac sodium by high-performance liquid chromatography in 0, 1 percent eyedrops

El diclofenaco de sodio es un medicamento que se indica para los tratamientos posoperatorios de la inflamación del segmento anterior del ojo, la inhibición de la miosis pre y posoperatoria de cataratas, el tratamiento sintomßtico de las conjuntivitis crónicas no infecciosas y de la inflamación ocular, del dolor ocular y fotofobia poscirugía refractiva. En este trabajo se desarrolló y validó un método analítico por cromatografía líquida de alta resolución, para el control de la calidad y los estudios de estabilidad del diclofenaco de sodio 0,1 por ciento, colirio. El método se basó en la separación del principio activo a través una columna cromatogrßfica Lichrospher 100 RP-8 endcapped (5 µm) (250 x 4 mm), con detección UV a 254 nm, para lo cual se empleó una fase móvil compuesta por solución de hidrógeno fosfato de sodio a pH 2,5:metanol, en proporción 34:60. La curva de calibración se realizó en el intervalo de 60 al 140 por ciento, donde fue lineal con un coeficiente de correlación igual a 0,9995; la prueba estadística para el intercepto y la pendiente se consideró no significativa. Se obtuvo un recobrado del 100,25 por ciento en el intervalo de concentraciones estudiados y las pruebas de Cochran´(G) y Student´s (t) resultaron no significativas. El coeficiente de variación en el estudio de la repetibilidad fue igual a 0,39 por ciento para las 6 réplicas ensayadas, mientras que en los análisis de la precisión intermedia las pruebas de Fischer y Student fueron no significativas. El método analítico resultó lineal, preciso, específico y exacto en el intervalo de concentraciones estudiadas.

Diclofenac sodium is a drug prescribed in eye anterior segment inflammation postoperative treatments, preoperative and postoperative cataract miosis inhibition, symptomatic treatment of non-infectious chronic conjunctivitis, of ocular inflammation, of ocular pain, and of refractory postsurgical photophobia. In present paper we developed and validated an analytical method by high-performance liquid chromatography to quality control, and stability studies of Diclofenac sodium of 1 percent eyedrops. Method was based on active principle separation through endcapped 1 00RP-8 Lichrospher chromatographic column (5 µ) (250 x 4 mm) using UV detection to 254 nm, thus using a mobile phase including sodium a solution of hydrogen phosphate to a 2.5 pH: methanol in a 34:60 ratio. Calibration curve was plotted during the interval of 60 to 140 percent where it was linear with a correlation coefficient equal to 0.9995; statistic test for interception and slope was considered as non-significant. We achieved a recovery rate of 100.25 percent during study concentration interval, and Cochran (G) and Student (t) tests were not significant. Variation coefficient in repeating study was equal to 0.39 percent for the 6 assayed replica, whereas in average precision analysis Fischer and Student tests were non-significant. Analytical method was linear, precise, specific and exact during the interval of study concentrations.