Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in healthy volunteers of both sexes

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable

Avaliação da qualidade microbiológica de cápsulas e chás de plantas utilizadas na assistência ao tratamento da obesidade / Microbiological quality evaluation of herbal capsules and teas to assist the treatment of obesity

O uso de plantas diuréticas e laxativas é uma alternativa medicamentosa para muitas pessoas que objetivam o emagrecimento com menores efeitos adversos. A avaliação microbiológica é um requisito essencial para a garantia de qualidade dos produtos. A finalidade deste trabalho foi avaliar a qualidade microbiológica de cápsulas e chás de alcachofra (Cynara scolymus L.), centella asiática (Hydrocotile asiatica L.), fucus (Fucus vesiculosus L.), e sene (Cassia acutifolia Delile), através da contagem de micro-organismos viáveis totais e pesquisa de patógenos. Na contagem de micro-organismos viáveis, os chás analisados foram aprovados, pois apesar de apresentarem uma carga microbiana elevada, esta se encontrava dentro das especificações, entretanto, 16,66% e 66,66% das cápsulas analisadas foram reprovadas por apresentaram quantidades superiores de bactérias e fungos, respectivamente. Na pesquisa de patógenos, 76% das amostras (88% dos chás e 58% das cápsulas) apresentaram um ou mais de um tipo de micro-organismo. Salmonella sp. esteve presente em 33% das amostras evidenciando a qualidade microbiológica insatisfatória dos produtos encontrados no mercado. Estes resultados demonstram a necessidade da realização do controle de qualidade tanto das matérias-primas vegetais, quanto dos produtos acabados, através do controle e fiscalização rigorosa, com adoção de medidas regulamentadoras e educativas.

The use of laxative and diuretic herbal drugs is an alternative therapy for many people looking for loosing weight with fewer side effects. The microbiological evaluation is an essential requirement for the quality assurance of products. This study aimed to evaluate the microbial quality of artichoke (Cynara scolymus L.), centella (Hydrocotile asiatica L.), fucus (Fucus vesiculosus L.), and Senna (Cassia acutifolia Delile) capsules and teas, by counting the total viable aerobic microorganisms and through tests for specified microorganisms. On the total viable aerobic microorganisms count, the teas analyzed were approved, because although they had a high microbial load, this was in accordance with the specifications, however 16.66% and 66.66% of the capsules analyzed were rejected because they presented higher amounts of bacteria and fungi, respectively. In relation to the tests for specified microorganisms, 76% of the samples (88% of the teas and 58% of the capsules) presented one or more than one type of microorganisms. Salmonella sp. was present in 33% of the samples, showing the unsatisfactory microbial quality of the products in the market. These results demonstrate the necessity of performing quality control both on herbal raw material and finished products, through a rigorous control and inspection, adopting regulatory and educational measures.

Formulation and evaluation of carvedilol microcapsules using Eudragit NE30D and sodium alginate

Inclusion complexes of carvedilol(CR) with hydroxyl propyl beta-cyclodextrin (HPBCD) was prepared using co-grinding technique. Then, the inclusion complex was microencapsulated using combinations of Eudragit NE30D (EU) and sodium alginate (SA) utilizing orifice gelation technique. The formulations were analysed by using Scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR), Differential scanning Calorimetry (DSC) and X-ray diffractometer (XRD) and also evaluated for particle size, encapsulation efficiency, production yield, swelling capacity, mucoadhesive properties, zeta potential and drug release. The microcapsules were smooth and showed no visible cracks and extended drug release of 55.2006% up to 12 hours in phosphate buffer of pH 6.8, showing particle size within the range of 264.5-358.5 µm, and encapsulation efficiency of 99.337±0.0100-66.2753±0.0014%.The in vitro release data of optimized batch of microcapsules were plotted in various kinetic equations to understand the mechanisms and kinetics of drug release, which followed first order kinetics, value of "n" is calculated to be 0.459 and drug release was diffusion controlled. The mice were fed with diet for inducing high blood pressure and the in vivo antihypertensive activity of formulations was carried out administering the optimized formulations and pure drug separately by oral feeding and measured by B.P Monwin IITC Life Science instrument and the results indicated that the bioavailability of carvedilol was increased both in vitro and in vivo with the mucoadhesive polymers showing primary role in retarding the drug release.

Prepararam-se complexos de carvedilol (CR) com hidroxipropil beta-ciclodextrina (HPBCD), utilizando a técnica de co-moagem. O complexo de inclusão foi microencapsulado empregando-se associações de Eudragit NE30D (EU) e alginato de sódio (AS), utilizando a técnica de gelificação de orifício. As formulações foram analisadas utilizando-se microscopia eletrônica de varredura (SEM), espectroscopia no infravermelho com Transformada de Fourier, calorimetria diferencial de varredura (DSC) e difratometria de raios X (XDR) e, também, avaliadas por tamanho de partícula, eficiência de encapsulação, rendimento de produção, capacidade de inchamento, propriedades mucoadesivas, potencial zeta e liberação do fármaco. Obtiveram-se microcápsulas lisas e sem fendas visíveis, com liberação prolongada do fármaco de 55,2006% em 12 horas em tampão fosfato pH 6,8, com tamanho de partículas na faixa de 264,5-358,5 mm e eficiência de encapsulação de 99,3337±0,0100-66,2753±0,0014%. Os dados de liberação in vitro de lote otimizado de microcápsulas foram plotados em várias equações cinéticas para se entender os mecanismos e a cinética de liberação do fármaco, que é de primeira ordem, o valor de "n" foi de 0,459 e a liberação do fármaco foi por difusão controlada. Os camundongos foram alimentados com dieta para induzir pressão sanguínea alta e a atividade anti-hipertensiva in vivo das formulações foi obtida por administração de formulações otimizadas e fármaco puro, separadamente, por via oral e medida pelo equipamento BP Monwin IITC Life Science. Os resultados mostraram que a biodisponibilidade do carvedilol aumentou tanto in vitro quanto in vivo com os polímeros mucoadesivos, mostrando papel principal no retardamento da liberação do fármaco.

Characterisation and applications of microcapsules obtained by interfacial polycondensation.

This review highlights the materials, mechanisms and applications of microencapsulation by interfacial polycondensation in different areas. This technology entraps active ingredients inside microcapsules/microspheres, having an average diameter ranging from nanosize to several 100 µ. Polycondensation reactions take place at the boundary of two phases to form the shells of microcapsules or matrix microspheres. The emulsion can be classified into three types: water-in-oil, oil-in-water and oil-in-oil. According to the hydrophilic-lipophilic property of core phase, different active substances, such as proteins, enzymes, insecticides, herbicides, vitamins, catalysts, drugs, essential oils, dyes and phase change materials, have been successfully incorporated into different microcapsules/microspheres. Based on the shell-forming materials, this technology is capable of preparing polyamine, polyurea, polyurethane, polythiourea, polyester, polyepoxide, polyacrylamide and polysiloxane microcapsules. Over the past two decades, microcapsules prepared by interfacial polycondensation have been widely used in carbonless paper, cosmetics, pharmacy, agriculture, energy storage/transfer, thermal insulation/regulation and information and magnetic recording.

[Eurand Minitabs--the innovative application formula of a pancreatic enzyme complex (Pangrol 10,000, 25,000)]. / Eurand Minitabs--innowacyjna formula aplikacji kompleksu enzymatycznego pankreatyny (Pangrol 10,000, 25,000).

Modern technology of solid oral drug forms, through the application of macromolecular polymers, generates a number of new formulation solutions. New technologies provide optimal parameters for the release of biologically active substances, increasing by these means pharmacotherapeutic effectiveness of a medicinal product. Basic properties of the innovative Eurand Minitabs technology, making possible the tableting of technologically and applicatively labile substances such as a pancreatic enzyme complex were dicussed. The application of encapsulated minitablets coated with a methacrylic acid copolymer guarantees an optimal range of lipase pharmacological activity.

Medical devices; gastroenterology-urology devices; classification of the ingestible telemetric gastrointestinal capsule imaging system. Final rule.

The Food and Drug Administration (FDA) is classifying the ingestible telemetric gastrointestinal capsule imaging system device into class II (special controls). The special controls that will apply to this device are set forth below. The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the amendments), the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997 (FDAMA). The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

Comparison of classification approaches applied to NIR-spectra of clinical study lots.

NIR-spectroscopy combined with pattern recognition approaches is applied to classify samples of clinical study lots in the pharmaceutical industry. The performance of linear discriminant analysis (LDA), quadratic discriminant analysis (QDA) and K-nearest neighbour (KNN) method is evaluated on a tablet data set and a capsule data set. To establish a classification model a strategy is followed, which is described in this work. Frequently, in the pharmaceutical industry, several batches of the same clinical study lot are produced. We tested whether it is possible to merge several batches in one class for modelling or, instead, whether it is necessary to model each batch individually.

Evaluación in vitro de la viabilidad y proliferación de fibroblastos de la Cápsula de Tenon humana: expuestos a 5-fluorouracilo y mitomicina C / Evaluation in vitro of the viability and proliferation of fibroblasts of Human Tenon capsule: expose to 5-fluororacil and mitomicyn C

En este trabajo reportamos los resultados de un estudio prospectivo acerca del efecto del 5-Fluorouracilo (5-Fu) y la Mitomicina C (MMC) sobre los fibroblastos provenientes de la cápsula de Tenon humana. El estudio fue realizado en pacientes del Servicio de Oftalmología del Hospital "F.A. Rísquez", Caracas, Venezuela. Los fibroblastos cultivados y expuestos a 5-FU y MMC en diferentes concentraciones y con diferentes tiempos de exposición. La viabilidad celular fue evaluada por el método del MTT y la proliferación de fibroblastos fue estudiada por cintaje celular con la cámara de Newbauer. Encontramos que la toxicidad celular fue mayor con el uso de la MMC que con el 5-FU, pero nunca mayor del 30 por ciento. La citotoxicidad relacionada con la concentración del 5-FU fue 12,7 por ciento a 14,3 por ciento en comparación con una citotoxicidad de 8.8 a 20.5 por ciento de la MMC. La citotoxicidad del 5-FU y la MMC fue directamente proporcional al tiempo de exposición. La inhibición de la proliferación de fibroblastos de la Cápsula de Tenon Humana fue mayor con la MMC que con el 5-FU. La toxicidad celular puede ser modulada más por la concentración de la droga que por el tiempo de exposición