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ABSTRACT BACKGROUND: Rutin is a flavonol glycoside that can be found in a wide variety of vegetables and has activity, anti-cancer, anti-inflammatory and anti-diabetic properties. OBJECTIVE: This study investigated the effect of rutin oral administration on Wistar rats submitted to hepatic hyperplasia after partial hepatectomy (PH). METHODS: To achieve this, we considered the analysis of hepatic hyperplastic and plasma biochemical activity of Wistar rats, subjected to treatment with rutin 40 mg/kg/day for 10 days in group 1 (G1) or saline in group 2 (G2), followed by partial hepatectomy. RESULTS: The results indicated an increase in the number of mitoses after 24 hours and 48 hours (P=0.0022 and P=0.0152, respectively) of PH in the group that received rutin, as well as an increase in AST serum levels after 24 hours (P=0.0159) and 48 hours (P=0.0158) and alkaline phosphatase after 24 hours (P=0.015) in the same group, in relation to the respective controls. The group that received rutin showed a more evident variation than the control group when comparing the 24 hour and 48 hour results regarding AST, number of mitoses and number of apoptosis (P<0.005). CONCLUSION: It was concluded that rutin intervened in hepatic hyperplasia after 24 hours and 48 hours of PH, favoring hepatic hyperplasia.

RESUMO CONTEXTO: A rutina é um flavonoide que pode ser encontrado em grande variedade de vegetais e apresenta atividades anticâncer, anti-inflamatória e antidiabética. OBJETIVO: O objetivo deste estudo foi investigar o efeito da administração oral de rutina sobre a hiperplasia hepática em ratos Wistar submetidos à hepatectomia parcial. MÉTODOS: Foi realizada a análise da hiperplasia hepática e da bioquímica plasmática dos ratos Wistar tratados com rutina 40 mg/kg por 10 dias no grupo 1 (G1) ou salina no grupo 2 (G2), seguido da hepatectomia parcial. RESULTADOS: Os resultados indicaram aumento do número de mitoses após 24 e 48 horas (P=0,0022 e P=0,0152, respectivamente) da hepatectomia parcial no grupo que recebeu rutina, além de um aumento nos níveis séricos de AST após 24 horas (P=0,0159) e 48 horas (P=0,0158) e de fosfatase alcalina após 24 horas (P=0,015) no mesmo grupo, em relação aos respectivos controles. O grupo que recebeu rutina mostrou variação mais evidente do que o grupo controle quando se comparou os resultados de 24 horas e 48 horas em relação a AST, número de mitoses e número de apoptoses (P<0,005). CONCLUSÃO: Foi possível concluir que a rutina interferiu na hiperplasia hepática após 24 e 48 horas após a hepatectomia parcial, favorecendo a hiperplasia hepática.

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OBJECTIVES: To evaluate the microbiological and physicochemical compatibility of commonly used proton pump inhibitors (PPIs) esomeprazole, lansoprazole, omeprazole and pantoprazole compounded at a single concentration using SyrSpend SF Alka and stored at refrigerated temperatures (omeprazole was also stored at room temperature because it has the most widespread use). METHODS: Compatibility was assessed by measuring the per cent recovery at varying time points throughout a 90-day period. Quantification of the APIs was performed by a validated high performance liquid chromatography (HPLC-UV) method. This same assay was also used to determine the dosage content uniformity of the suspensions. Microbiological stability ('test in use') was assessed during 60 days and total aerobic microbial count (TAMC), total combined yeasts and moulds count (TYMC), detection of Escherichia coli and pH determination were performed. Antimicrobial effectiveness testing was determined following European Pharmacopoeia guidelines. RESULTS: Beyond-use dates of maximum 60 days for omeprazole (5 mg/mL), pantoprazole (3 mg/mL) and esomeprazole (3 mg/mL) were established. All suspensions that met the physicochemical criteria for stability also met the content uniformity criteria. The suspensions showed no antimicrobial efficiency against bacteria, yeasts and moulds as SyrSpend SF Alka is an unpreserved vehicle, but the 'test in use' showed that the suspensions can remain microbiologically stable for up to 60 days. CONCLUSIONS: SyrSpend SF Alka can be used to compound palatable (taste-masking properties) preservative-free oral suspensions with almost all commonly used PPIs.

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Abstract Aleurites moluccanus L. (Willd.), Euphorbiaceae, is a tree that is native to Indonesia and India. Various parts of this tree are commonly used in traditional medicine to treat pain, fever, inflammation, hepatitis, gastric ulcer and other ailments. An oral suspension containing dried extract of A. moluccanus was developed and in vivo anti-inflammatory activity was evaluated. Extract 100 and 50 mg/ml loaded oral suspensions were prepared using different suspending agents. The formulations were analysed by their appearance, pH, density, redispersion time, rate of settling, rheological behaviour, distribution of particle size and zeta potential. The dose uniformity was determined by measuring the content of total phenolic compounds expressed in swertisin by a validated HPLC method, as well as the dissolution profile. The stability of oral suspensions was analysed in accelerated studies (40 °C for 6 months). The anti-inflammatory activity was analysed using an in vivo paw oedema model. The taste and odour of the suspensions were shown to be characteristic of the extract. Carmellose sodium (CS; 0.5%) and microcrystalline cellulose and carmellose sodium mixture (MCCS; 1%) showed better physical behaviour. The content of total phenolic compounds was 1.6 mg/ml and approximately 100% of the total phenolic compounds dissolved within 10 min. During the stability study, the formulations were approved by their physical–chemical properties and were shown to lose 12–14% of total phenolic compounds at 40 °C after 6 months. Suspensions containing 50 mg/ml of standardised dried extract inhibited around 35 ± 7.6% of paw oedema. Formulations containing CS showed more anti-inflammatory activity. Suspensions containing dry extract of A. moluccanus were successfully obtained and showed physical and physical–chemistry properties that were appropriate and characteristic of this dosage form, suitable for administration in paediatric and elderly populations, making this an alternative to tablets.

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A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations.

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The present study describes the development and validation of an in vitro dissolution method for evaluation to release diclofenac potassium in oral suspension. The dissolution test was developed and validated according to international guidelines. Parameters like linearity, specificity, precision and accuracy were evaluated, as well as the influence of rotation speed and surfactant concentration on the medium. After selecting the best conditions, the method was validated using apparatus 2 (paddle), 50-rpm rotation speed, 900 mL of water with 0.3% sodium lauryl sulfate (SLS) as dissolution medium at 37.0 ± 0.5°C. Samples were analyzed using the HPLC-UV (PDA) method. The results obtained were satisfactory for the parameters evaluated. The method developed may be useful in routine quality control for pharmaceutical industries that produce oral suspensions containing diclofenac potassium.

O presente estudo descreve o desenvolvimento e validação de um método de dissolução in vitro para avaliação da liberação de diclofenaco potássico suspensão oral. O teste de dissolução foi desenvolvido e validado de acordo com as diretrizes internacionais. Parâmetros como linearidade, especificidade, precisão e exatidão foram avaliados, bem como a influência da velocidade de rotação e a concentração de tensoativono meio. Depois de selecionar as melhores condições, o método foi validado usando o aparato 2 (pás), velocidade de rotação de 50 rpm, 900 mL de água com 0,3% de lauril sulfato de sódio (LSS) como meio de dissolução a 37,0 ± 0,5 ºC. As amostras foram analisadas pelo método de CLAE-UV (PDA). Os resultados obtidos foram satisfatórios para os parâmetros avaliados. O método desenvolvido pode ser útil na rotina de controle de qualidade para as indústrias farmacêuticas que produzem suspensões orais contendo diclofenaco potássico.

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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.

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INTRODUCCIÓN: la Organización Mundial de la Salud (OMS) declaró la pandemia de gripe A H1N1 en 2009. La autoridad sanitaria argentina promovió el desarrollo y validación de un método de control de calidad de productos farmacéuticos que contenían oseltamivir como principio activo. OBJETIVO: Desarrollar y validar un método de valoración para oseltamivir en las formas farmacéuticas de cápsulas y polvo para suspensión oral. MÉTODOS: La valoración de oseltamivir fue realizada mediantecromatografía líquida de alta eficacia (CL AE), con elusión isocrática a una temperatura de 50°C, columna Phenomenex Luna RP-8, solución reguladora de acetato pH 5,39 y metanol como fase móvil. La detección se realizó con detector de arreglo de diodos a 230 nm. El método fue validado mediante la evaluación de especificidad, retención en filtros, estabilidad de las soluciones, linealidad, exactitud, precisión y robustez. RESULTADOS: Se desarrolló y validó un método por CLAE para la valoración de oseltamivir, el cual fue aplicado con resultados satisfactorios en el análisis de 11 especialidades medicinales de laboratorios nacionales e internacionales. CONCLUSIONES: El método desarrollado puede aplicarse para el control de todos los productos del mercado argentino en sus dos formas farmacéuticas.

INTRODUCTION: Tthe World Health Organization(WHO) declared the pandemic influenza A H1N1 virus infection in 2009. Argentine health authorities promoted the development and validation of a quality control method for pharmaceutical products containing oseltamivir as active ingredient. OBJECTIVE: To develop and validate a method for oseltamivir quantitative determination in the pharmaceutical dosage forms of capsules and powder for oral suspension. METHODS: The determination of oseltamivir was performed using a high performance liquid chromatography (HPLC) method under an isocratic elution, at a temperature of 50°C with a RP-8 Phenomenex Luna column and a mobile phase containing acetate buffer pH 5.39 and methanol. The detection was performed at 230nm with a diodearray detector. The method was validated by evaluating specificity, filter retention, solution stability, linearity, accuracy, precision and robustness. RESULTS: An HPLC method was developed and validated for quantitative determination of oseltamivir, and it was successfully applied in the analysis of eleven medical products from national and international laboratories. CONCLUSIONS:The method developed can be applied for control of all products on the Argentine market in its two pharmaceutical forms.

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