Controlo de qualidade microbiológica na indústria farmacêutica

O presente Relatório de Estágio teve como objectivo analisar e discutir as competências adquiridas e desenvolvidas, durante o estágio, no controlo da qualidade microbiológica na indústria farmacêutica O estágio, foi realizado no Laboratório de Microbiologia dos Laboratórios Atral, Grupo AtralCipan, localizado na Vala do Carregado, Castanheira do Ribatejo. Este teve a duração de aproximadamente dez meses e meio, com data de início a 21 de Setembro de 2011 e final de 10 de Agosto de 2012. Numa fase inicial, foram adquiridas as aptidões necessárias para a aplicação das metodologias realizadas no laboratório de microbiologia com o estudo das normas, procedimento e legislação aplicada, com foco na importância das farmacopeias na indústria farmacêutica e formação para a realização de ensaios em Áreas de Processamento Asséptico, conhecendo e compreendendo os procedimentos a ter nestas. Uma das principais metodologias realizadas, e desenvolvida neste relatório, compreendeu a análise de produtos farmacêuticos estéreis, com a aplicação de Testes de Esterilidade, pelo método de STERITEST e método Directo, com resultados que demonstraram a importância destas técnicas, da avaliação do ambiente em que são realizadas e do operador que as executa. Os Testes de Promoção de Crescimento, foram também explorados neste trabalho, realizados não só para avaliação dos meios de cultura, onde foi possível analisar os requisitos e resultados obtidos, como também para validação de metodologias, nomeadamente, na validação de meios e fluidos de marcas diferentes para utilização no método STERITEST e na validação do método de filtração de membrana para Enumeração Microbiana de um produto não estéril. Estas validações possibilitaram a redução de custos e melhoria das condições da análise e metodologias aplicadas. Com a realização do estágio foi possível adquirir aptidões práticas, que aliadas ao conhecimento teórico obtido no mestrado, proporcionaram um crescimento a nível pessoal, científico e profissional.

Mergers and acquisitions as strategies of business expansion in the pharmaceutical industry

Introduction: The present paper deals with the issue of the increasing usage of corporation mergers and acquisitions strategies within pharmaceutical industry environment. The aim is to identify the triggers of such business phenomenon and the immediate impact on the financial outcome of two powerful biopharmaceutical corporations: Pfizer and GlaxoSmithKline, which have been sampled due to their successful approach of the tactics in question. Materials and Methods: In order to create an overview of the development steps through mergers and acquisitions, the historical data of the two corporations has been consulted, from their official websites. The most relevant events were then associated with adequate information from the financial reports and statements of the two corporations indulged by web-based financial data providers. Results and Discussions: In the past few decades Pfizer and GlaxoSmithKline have purchased or merged with various companies in order to monopolize new markets, diversify products and services portfolios, survive and surpass competitors. The consequences proved to be positive although this approach implies certain capital availability. Conclusions: Results reveal the fact that, as far as the two sampled companies are concerned, acquisitions and mergers are reactions at the pressure of the highly competitive environment. Moreover, the continuous diversification of the market’s needs is also a consistent motive. However, the prevalence and the eminence of mergers and acquisition strategies are conditioned by the tender offer, the announcer’s caliber, research and development status and further other factors determined by the internal and external actors of the market.

Feedback regarding students initial pharmaceutical internship from the University of Medicine and Pharmacy, Cluj-Napoca

Introduction/Aims: The purpose of the study is to evaluate the perception of the organization, the development and the evaluation of the initial stage in the internship of students, in order to improve these activities and to establish the adequate objectives in accordance with the changes concerning the concept of modern pharmacy. Materials and methods: An online survey was made using Google Docs ® -Create Form extension. All results were accumulated and computed using Microsoft Excel ®. The questionnaire consisted of 11 questions, structured on several levels: the objectives and how they can be achieved, internship organization, the internship training (effective participation in specific activities and integration in the pharmaceutical activity), the assessment, the profile of tutor / pharmacy. The questionnaire was completed by students from the Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" Cluj Napoca, Romania. Results and discussions. The study was conducted on 308 students (60% of all students from the study years II-IV. 90% of the respondents had actually participated in the internship, whilst 10% only formally participated in this activity. The main responsibilities of the students were: storage and reception of pharmaceutical products (94%, respectively 79%) and working with the receipts (57%). Most of the students appreciate that they were integrated into the work in the pharmacy, this being due largely pharmacist tutor, who expressed interest and ability in mentoring activities. They appreciated that the role of tutor requires 3-5 years of professional experience. In terms of the internship objectives, these should aim at applying the knowledge gained until the graduation year, but also familiarization with activities which might turn into applications for the coming years. 43% of students believe that only 25% of the theoretical knowledge was useful during the internship. 90 % of the total questioned considered useful to develop a practice guideline adapted to the year of study. Conclusions. The professional training of the future pharmacist’s students depends largely on experience gained by students during the internship activity. Feed-back from the students’ shows that they are aware of the usefulness of the internship, but believe the objectives must be updated and a better correlation between work in pharmacy and theoretical knowledge has to be made. A first step is to develop a practical guide adapted to each year of study. The involvement of the tutor pharmacist is also essential to the success of this activity

Development of electrochemical methods for determination of tramadol - analytical application to pharmaceutical dosage forms

A square-wave voltammetric (SWV) method and a flow injection analysis system with amperometric detection were developed for the determination of tramadol hydrochloride. The SWV method enables the determination of tramadol over the concentration range of 15-75 µM with a detection limit of 2.2 µM. Tramadol could be determined in concentrations between 9 and 50 µM at a sampling rate of 90 h-1, with a detection limit of 1.7 µM using the flow injection system. The electrochemical methods developed were successfully applied to the determination of tramadol in pharmaceutical dosage forms, without any pre-treatment of the samples. Recovery trials were performed to assess the accuracy of the results; the values were between 97 and 102% for both methods.

Direct electroanalytical determination of fluvastatin in a pharmaceutical dosage form: batch and flow analysis

The reduction of luvastatin (FLV) at a hanging mercury-drop electrode (HMDE) was studied by square-wave adsorptive-stripping voltammetry (SWAdSV). FLV can be accumulated and reduced at the electrode, with a maximum peak current intensity at a potential of approximately 1.26V vs. AgCl=Ag, in an aqueous electrolyte solution of pH 5.25. The method shows linearity between peak current intensity and FLV concentration between 1.0 10 8 and 2.7 10 6 mol L 1. Limits of detection (LOD) and quantification (LOQ) were found to be 9.9 10 9 mol L 1 and 3.3 10 8 mol L 1, respectively. Furthermore, FLV oxidation at a glassy carbon electrode surface was used for its hydrodynamic monitoring by amperometric detection in a flow-injection system. The amperometric signal was linear with FLV concentration over the range 1.0 10 6 to 1.0 10 5 mol L 1, with an LOD of 2.4 10 7 mol L 1 and an LOQ of 8.0 10 7 mol L 1. A sample rate of 50 injections per hour was achieved. Both methods were validated and showed to be precise and accurate, being satisfactorily applied to the determination of FLV in a commercial pharmaceutical.

Electroanalytical determination of codeine in pharmaceutical preparations

A square wave voltammetric (SWV) method and a flow injection analysis systemwi th electrochemical detection (FIA-EC) using a glassy carbon electrode were evaluated for the determination of codeine in pharmaceutical preparations. The interference of several compounds, such as acetaminophen,guaiacol, parabens, ephedrine, acetylsalicylic acid and caffeine, that usually appear associated with codeine pharmaceutical preparations was studied. It was verified that these electroanalytical methods could not be used with acetaminophen present in the formulations and that with guaiacol, parabens or ephedrine present the use of the FIA-EC system was impracticable. A detection limit of 5 µmol L- 1 and a linear calibration range from 40 to 140 µmol L- 1 was obtained with the SWV method. For the flow injection analysis procedure a linear calibration range was obtained from 7 to 50 µmol L- 1 with a detection limit of 3 µmol L- 1 and the FIA-EC systemallowed a sampling rate of 115 samples per hour. The results obtained by the two methods, SWV and FIA-EC, were compared with those obtained using reference methods and demonstrated good agreement, with relative deviations lower than 4%.

Electrochemical determination of citalopram by adsorptive stripping voltammetry–determination in pharmaceutical products

The electrochemical behavior of citalopram was studied by square-wave and square-wave adsorptive-stripping voltammetry (SWAdSV). Citalopram can be reduced and accumulated at a mercury drop electrode, with a maximum peak current intensity being obtained at a potential of approximately -1.25V vs. AgCl/Ag, in an aqueous electrolyte solution of pH 12. A SWAdSV method has been developed for the determination of citalopram in pharmaceutical preparations. The method shows a linear range between 1.0x10-7 and 2.0x10-6 mol L-1 with a limit of detection of 5x10-8 mol L-1 for an accumulation time of 30 s. The precision of the method was evaluated by assessing the repeatability and intermediate precision, achieving good relative standard deviations in all cases (≤2.3%). The proposed method was applied to the determination of citalopram in five pharmaceutical products and the results obtained are in good agreement with the labeled values.

Citrate selective electrodes for the flow injection analysis of soft drinks, beers and pharmaceutical products

Aiming the establishment of simple and accurate readings of citric acid (CA) in complex samples, citrate (CIT) selective electrodes with tubular configuration and polymeric membranes plus a quaternary ammonium ion exchanger were constructed. Several selective membranes were prepared for this purpose, having distinct mediator solvents (with quite different polarities) and, in some cases, p-tert-octylphenol (TOP) as additive. The latter was used regarding a possible increase in selectivity. The general working characteristics of all prepared electrodes were evaluated in a low dispersion flow injection analysis (FIA) manifold by injecting 500µl of citrate standard solutions into an ionic strength (IS) adjuster carrier (10−2 mol l−1) flowing at 3ml min−1. Good potentiometric response, with an average slope and a repeatability of 61.9mV per decade and ±0.8%, respectively, resulted from selective membranes comprising additive and bis(2-ethylhexyl)sebacate (bEHS) as mediator solvent. The same membranes conducted as well to the best selectivity characteristics, assessed by the separated solutions method and for several chemical species, such as chloride, nitrate, ascorbate, glucose, fructose and sucrose. Pharmaceutical preparations, soft drinks and beers were analyzed under conditions that enabled simultaneous pH and ionic strength adjustment (pH = 3.2; ionic strength = 10−2 mol l−1), and the attained results agreed well with the used reference method (relative error < 4%). The above experimental conditions promoted a significant increase in sensitivity of the potentiometric response, with a supra-Nernstian slope of 80.2mV per decade, and allowed the analysis of about 90 samples per hour, with a relative standard deviation <1.0%.

Bridging the gap between closed and open data. System proposal for the Portuguese Legislation

Esta dissertação apresenta uma proposta de sistema capaz de preencher a lacuna entre documentos legislativos em formato PDF e documentos legislativos em formato aberto. O objetivo principal é mapear o conhecimento presente nesses documentos de maneira a representar essa coleção como informação interligada. O sistema é composto por vários componentes responsáveis pela execução de três fases propostas: extração de dados, organização de conhecimento, acesso à informação. A primeira fase propõe uma abordagem à extração de estrutura, texto e entidades de documentos PDF de maneira a obter a informação desejada, de acordo com a parametrização do utilizador. Esta abordagem usa dois métodos de extração diferentes, de acordo com as duas fases de processamento de documentos – análise de documento e compreensão de documento. O critério utilizado para agrupar objetos de texto é a fonte usada nos objetos de texto de acordo com a sua definição no código de fonte (Content Stream) do PDF. A abordagem está dividida em três partes: análise de documento, compreensão de documento e conjunção. A primeira parte da abordagem trata da extração de segmentos de texto, adotando uma abordagem geométrica. O resultado é uma lista de linhas do texto do documento; a segunda parte trata de agrupar os objetos de texto de acordo com o critério estipulado, produzindo um documento XML com o resultado dessa extração; a terceira e última fase junta os resultados das duas fases anteriores e aplica regras estruturais e lógicas no sentido de obter o documento XML final. A segunda fase propõe uma ontologia no domínio legal capaz de organizar a informação extraída pelo processo de extração da primeira fase. Também é responsável pelo processo de indexação do texto dos documentos. A ontologia proposta apresenta três características: pequena, interoperável e partilhável. A primeira característica está relacionada com o facto da ontologia não estar focada na descrição pormenorizada dos conceitos presentes, propondo uma descrição mais abstrata das entidades presentes; a segunda característica é incorporada devido à necessidade de interoperabilidade com outras ontologias do domínio legal, mas também com as ontologias padrão que são utilizadas geralmente; a terceira característica é definida no sentido de permitir que o conhecimento traduzido, segundo a ontologia proposta, seja independente de vários fatores, tais como o país, a língua ou a jurisdição. A terceira fase corresponde a uma resposta à questão do acesso e reutilização do conhecimento por utilizadores externos ao sistema através do desenvolvimento dum Web Service. Este componente permite o acesso à informação através da disponibilização de um grupo de recursos disponíveis a atores externos que desejem aceder à informação. O Web Service desenvolvido utiliza a arquitetura REST. Uma aplicação móvel Android também foi desenvolvida de maneira a providenciar visualizações dos pedidos de informação. O resultado final é então o desenvolvimento de um sistema capaz de transformar coleções de documentos em formato PDF para coleções em formato aberto de maneira a permitir o acesso e reutilização por outros utilizadores. Este sistema responde diretamente às questões da comunidade de dados abertos e de Governos, que possuem muitas coleções deste tipo, para as quais não existe a capacidade de raciocinar sobre a informação contida, e transformá-la em dados que os cidadãos e os profissionais possam visualizar e utilizar.