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.

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.

Synthesis, characterization and antiproliferative activity on cancer cell lines of new ionic liquids from ampicillin

Ionic Liquids (ILs) are ionic compounds that possess melting temperature below 100ºC and they have been a topic of great interest since the mid-1990s due to their unique properties. The range of IL uses has been broadened, due to a significant increase in the variety of physical, chemical and biological ILs properties. They are now used as Active Pharmaceutical Ingredients (APIs) and recent interests are focused on their application as innovative solutions in new medical treatment and delivery options.1 In this work, our principal objective was the synthesis and investigation of physicochemical and medical properties of ionic liquids (ILs) and organic salts from ampicillin. This approach is of huge interest in pharmaceutical industry as cation and anion composition of ILs and organic salts can greatly alter their desired properties, namely the melting temperature and even synergistic effects can be obtained.2,3 For the synthesis of these compounds we used a recently developed method proposed by Ohno et al.4 for the preparation of quaternary ammonium and phosphonium hydroxides, that were neutralized by ampicillin. After purification we obtained pure ILs and salts in good yields. These ILs shows good antimicrobial and antifungal activities. As it is well known that some ionic liquids containing phosphonium and ammonium cation also shows anti-cancer activity1,5 we also decided to study these compounds against some cancer cell lines.

Avaliação ecotoxicológica de solos contaminados por ibuprofeno

Os produtos farmacêuticos são substâncias químicas muito utilizados em medicina, veterinária e ainda na agricultura. Nos anos 90, foi descoberta a presença de fármacos em meio aquático, verificando-se que a sua remoção nas Estações de Tratamento de Águas Residuais (ETAR) não era completa. Durante as duas últimas décadas foi identificada a presença de mais de oitenta compostos no meio ambiente e actualmente são considerados poluentes emergentes. Podem contaminar solos e águas, depois de serem usados e excretados (inalterados ou metabolizados) por humanos e animais, ou quando são indevidamente lançados directamente no meio ambiente. Os estudos ecotoxicológicos efectuados com estes poluentes têm sido direccionados, sobretudo, para as águas, existindo uma ausência de trabalhos sobre solos. O Ibuprofeno (IB) é um anti-inflamatório não esteróide, utilizado também como analgésico e antipirético, sendo um dos produtos farmacêuticos mais vendidos em todo o mundo, o que justifica a sua forte presença no meio ambiente. Por isso, e dada a ausência de trabalhos ecotoxicológicos de solos contaminados por fármacos, o IB foi o produto farmacêutico selecionado para a realização deste trabalho. A ecotoxicidade pode ser avaliada através de bioensaios. Estes têm a capacidade de avaliar a toxicidade de uma determinada substância de forma global, usando organismos vivos que funcionam como bio-indicadores. O presente trabalho tem como objectivos avaliar o impacte causado nos solos pelo IB, testar a toxicidade de dois processos de descontaminação para remover o referido fármaco dos solos assim como avaliar a toxicidade provocada por águas residuais, de três unidades hospitalares e de uma indústria farmacêutica. Esta avaliação foi efectuada através de ensaios de toxicidade aguda de germinação e de alongamento de raiz de sementes de alface, variedade bola de manteiga (Lactuca sativa), em solo arenoso. Os ensaios de ecotoxicidade aguda em solos contaminados por IB foram realizados para uma gama de concentrações entre 0,1 e 1000 μg/L. Verificou-se uma redução do número de sementes germinadas e do comprimento médio da planta no solo contaminado com 0,5 e 20 μg/L de IB. No solo contaminado com 1000 μg/L de IB observou-se uma redução da germinação, acompanhada por uma indução de crescimento da raiz da espécie Lactuca sativa. Os dois tratamentos de descontaminação de solos, reagente de Fenton e Nanopartículas de ferro zero valente, revelaram toxicidade, tendo-se obtido uma percentagem de germinação entre 32,2 ± 3,5 e 48,5 ± 6,2 e inibição do crescimento da raiz do organismo teste em cerca de 85,0 %. Em relação às águas residuais hospitalares verificou-se uma redução da percentagem de germinação entre 31,1 ± 5,0 e 72,3 ± 12,4 e uma inibição do crescimento da raiz situada entre 13,0 ± 6,4 e 20,2 ± 10,0 %. Para a água residual industrial ocorreu uma inibição da percentagem de germinação de 60,5 ± 13,1, contudo nas plantas germinadas observou-se uma indução do crescimento da raiz de 14,9 ± 7,7 %.

Ligand-Induced structural changes in TEM‑1 probed by molecular dynamics and relative binding free energy calculations

The TEM family of enzymes has had a crucial impact on the pharmaceutical industry due to their important role in antibiotic resistance. Even with the latest technologies in structural biology and genomics, no 3D structure of a TEM- 1/antibiotic complex is known previous to acylation. Therefore, the comprehension of their capability in acylate antibiotics is based on the protein macromolecular structure uncomplexed. In this work, molecular docking, molecular dynamic simulations, and relative free energy calculations were applied in order to get a comprehensive and thorough analysis of TEM-1/ampicillin and TEM-1/amoxicillin complexes. We described the complexes and analyzed the effect of ligand binding on the overall structure. We clearly demonstrate that the key residues involved in the stability of the ligand (hot-spots) vary with the nature of the ligand. Structural effects such as (i) the distances between interfacial residues (Ser70−Oγ and Lys73−Nζ, Lys73−Nζ and Ser130−Oγ, and Ser70−Oγ−Ser130−Oγ), (ii) side chain rotamer variation (Tyr105 and Glu240), and (iii) the presence of conserved waters can be also influenced by ligand binding. This study supports the hypothesis that TEM-1 suffers structural modifications upon ligand binding.

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

Planning, Cooperation and Competition: A case study in industry and construction in a Portuguese Region

In the present paper we analyzed the behavior of firms in the construction and manufacturing sectors, located in the region of Vale do Sousa, in the north of Portugal. From the literature, even existing some disagreements, it is possible to conclude that planning is crucial for firms survival and growth. Cooperation is another aspect that the literature presents as an important factor for firms sustainability. It also plays a major role in competition, since firms are adopting coopetition strategies. By studying a sample of 251 firms, it was possible to realize, that the majority started their business without a formal planning, and they keep going without using it. In cooperation aspects, there is a lack of cooperation. It was possible to verify, that existing cooperation has some evidence but at a vertical level. These vertical relations were also identified in stakeholder’s involvement.

Espresso coffee residues: a valuable source of unextracted compounds

Espresso spent coffee grounds were chemically characterized to predict their potential, as a source of bioactive compounds, by comparison with the ones from the soluble coffee industry. Sampling included a total of 50 samples from 14 trademarks, collected in several coffee shops and prepared with distinct coffee machines. A high compositional variability was verified, particularly with regard to such water-soluble components as caffeine, total chlorogenic acids (CGA), and minerals, supported by strong positive correlations with total soluble solids retained. This is a direct consequence of the reduced extraction efficiency during espresso coffee preparation, leaving a significant pool of bioactivity retained in the extracted grounds. Besides the lipid (12.5%) and nitrogen (2.3%) contents, similar to those of industrial coffee residues, the CGA content (478.9 mg/100 g), for its antioxidant capacity, and its caffeine content (452.6 mg/100 g), due to its extensive use in the food and pharmaceutical industries, justify the selective assembly of this residue for subsequent use.

Valorização de subprodutos da vinha e do vinho: impacto do tempo e métodos de preservação nas suas características

Os polifenóis constituem um grupo biologicamente relevante de compostos naturais, que têm gerado um crescente interesse por parte dos consumidores e das indústrias alimentar, farmacêutica e de cosméticos. Os compostos fenólicos exibem uma vasta gama de propriedades fisiológicas, tais como anti-alérgica, anti-aterogénica, anti-inflamatória, anti-microbiana, antioxidante, anti-trombótica, possuindo efeitos cardio-protetores e vasodilatadores. Por conseguinte, o interesse na obtenção deste compostos ativos de uma forma fácil, barata e rápida tem vindo a aumentar. Uma das fontes de polifenóis são os subprodutos agrícolas, tais como os produtos derivados do vinho e/ou processamento de uvas. As folhas, os caules e os resíduos obtidos durante o processo de produção do vinho têm sido subutilizados, apesar de representarem uma boa fonte de compostos antioxidantes e bioativos. Portugal é um dos mais importantes países produtores de vinho, onde todos os anos são geradas várias toneladas de subprodutos associados a esta indústria. A extração, caracterização, quantificação e avaliação da atividade antioxidante de compostos bioativos extraídos destes subprodutos são, pois, tarefas importantes a fim de avaliar o potencial de utilização destes produtos como novas fontes de compostos antioxidantes. O objetivo deste trabalho foi quantificar e avaliar os teores de polifenóis de extratos preparados a partir de folhas e caules de videira, e bagaço, engaço e grainha de uva. Os parâmetros experimentais da extração foram otimizados, incluindo a proporção de solvente de extração (água/etanol), a temperatura e o tempo de extração. A quantificação dos polifenóis (como fenóis totais e flavonoides) foi efetuada por espetrofotometria de UV/Vis. Verificou-se que a melhor razão de solventes extratores foi de 50/50 (v/v) em água/etanol para todos os subprodutos estudados. No caso dos subprodutos folhas e caules, as condições ideais de extração foram obtidas quando se usou uma temperatura de 40ºC e um tempo de extração de 30 min. Para o bagaço, a temperatura ideal foi de 55ºC durante 5 min. Para o engaço e grainha a utilização de uma temperatura de 40ºC durante 5 min e 30 min, respetivamente, revelou-se o ideal para se obter os compostos. Com este trabalho conclui-se que os subprodutos da vinha e do vinho efetivamente possuem compostos de elevado valor e com capacidade antioxidante.

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%.

Cleanup of industrial effluents containing heavy metals: a new opportunity of valorising the biomass produced by brewing industry

Heavy metal pollution is a matter of concern in industrialised countries. Contrary to organic pollutants, heavy metals are not metabolically degraded. This fact has two main consequences: its bioremediation requires another strategy and heavy metals can be indefinitely recycled. Yeast cells of Saccharomyces cerevisiae are produced at high amounts as a by-product of brewing industry constituting a cheap raw material. In the present work, the possibility of valorising this type of biomass in the bioremediation of real industrial effluents containing heavy metals is reviewed. Given the autoaggregation capacity (flocculation) of brewing yeast cells, a fast and off-cost yeast separation is achieved after the treatment of metal-laden effluent, which reduces the costs associated with the process. This is a critical issue when we are looking for an effective, eco-friendly, and low-cost technology. The possibility of the bioremediation of industrial effluents linked with the selective recovery of metals, in a strategy of simultaneous minimisation of environmental hazard of industrial wastes with financial benefits from reselling or recycling the metals, is discussed.