Strategic development and physicochemical analysis of oral preparations for unstable drugs

Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.

Europäische Nachbarschaftspolitik:Entstehung, Effektivität, Herausforderungen

„Ich wünsche mir einen Ring von Freunden um die Europäische Union und ihre engsten Nachbarn herum, von Marokko bis Russland und zum Schwarzen Meer“, formulierte Kommissionspräsident Romano Prodi bereits im Jahr 2002. Für die Gestaltung kooperativer Beziehungen zu diesem Ring von Freunden ist die Europäische Nachbarschaftspolitik (ENP) das jüngste Instrument der Europäischen Union. Die Kooperationen erfolgen in einer Reihe verschiedener Politikfelder und sollen dazu dienen, Stabilität, Sicherheit und Wohlstand an den Außengrenzen der EU zu sichern. Ziel dieses Beitrags ist es, einen Überblick über die Europäische Nachbarschaftspolitik (ENP) zu geben, insbesondere über ihre Gründung und Entwicklung, ihre zentralen Institutionen und Entscheidungsprozesse sowie die Debatte um ihre Wirksamkeit. Der Beitrag schließt mit einem Überblick über Forschungslücken und offene Fragen, die weitere Forschungsarbeiten zur ENP anregen sollen.

Spondias tuberosa Arr. (UMBU): estudo fitoquímico e avaliação do potencial anti-inflamatório

Spondias tuberosa Arruda (Anacardiaceae) is a fruitful tree popularly known as umbuzeiro, tapereba or umbu. It is a native and endemic species from Brazil, widespread in Brazilian Northeast. The species is important in folk medicine of the semi-arid Northeast, where it is mainly used to treat various inflammatory conditions, digestive problems as well as viral and bacterial infections. However, despite the common use in folk medicine, there are scarce pharmacological and phytochemicals studies that afford scientific evidence to its popular use. Therefore, this study aimed to characterize the chemical markers in S. tuberosa leaves extract, obtained by maceration ethanol:water (70:30, [v/v]), and evaluate its anti-inflammatory potential in vivo. The phytochemical profile in TLC analysis suggested the occurence of the flavonoids rutin and isoquercitrin. HPLC analysis enabled us to confirm the presence of flavonoids and also, were detected the phenolic acids, chlorogenic acid and caffeic acid. In addition was developed and validated a HPLC method to evaluate the content of the identified compounds in S. tuberosa leaves extract according to RDC 899/2003 of ANVISA and ICH Guidelines 2005. In order to evaluate the anti-inflammatory potential of S. tuberosa leaves extract, the peritonitis and paw edema models induced by carrageenan were used, administration i.p. in mice. The results highlighted the anti-inflammatory property in vivo at 125, 250 and 500 mg/kg since a decrease in leukocyte influx to the site of inflammation, diameter of the edema and the level of myeloperoxidase were observed when compared to the drug control dexamethasone (2 mg/kg, i.p. route). Taken together, the results pointed out S. tuberosa as a potential species for developing phytotherapic derivatives in according to its popular use. With regard to the characterization markers, chlorogenic acid, caffeic acid, rutin and isoquercitrin were identified and quantified in Spondias tuberosa leaves extract so they could be used in quality control analyses of the raw material and extracts of this species.

Développement d’une lentille cornéenne médicamentée

L’utilisation de lentilles cornéennes peut servir à améliorer le profil d’administration d’un principe actif dans les yeux. Avec une efficacité d’administration de 5% par l’utilisation de gouttes, on comprend rapidement que l’administration oculaire doit être améliorée. Cette faible administration a donné naissance à plusieurs tentatives visant à fabriquer des lentilles cornéennes médicamentées. Cependant, à cause de multiples raisons, aucune de ces tentatives n’a actuellement été mise sur le marché. Nous proposons dans cette étude, une possible amélioration des systèmes établis par le développement d’une lentille cornéenne à base de 2-(hydroxyéthyle)méthacrylate (HEMA), dans laquelle des microgels, à base de poly N-isopropylacrylamide (pNIPAM) thermosensible encapsulant un principe actif, seront incorporé. Nous avons donc débuté par développer une méthode analytique sensible par HPCL-MS/MS capable de quantifier plusieurs molécules à la fois. La méthode résultante a été validée selon les différents critères de la FDA et l’ICH en démontrant des limites de quantifications et de détections suffisamment basses, autant dans des fluides simulés que dans les tissus d’yeux de lapins. La méthode a été validée pour sept médicaments ophtalmiques : Pilocarpine, lidocaïne, proparacaïne, atropine, acétonide de triamcinolone, timolol et prednisolone. Nous avons ensuite fait la synthèse des microgels chargés négativement à base de NIPAM et d’acide méthacrylique (MAA). Nous avons encapsulé une molécule modèle dans des particules ayant une taille entre 200 et 600 nm dépendant de la composition ainsi qu’un potentiel zêta variant en fonction de la température. L’encapsulation de la rhodamine 6G (R6G) dans les microgels a été possible jusqu’à un chargement (DL%) de 38%. L’utilisation des isothermes de Langmuir a permis de montrer que l’encapsulation était principalement le résultat d’interactions électrostatiques entre les MAA et la R6G. Des cinétiques de libérations ont été effectuées à partir d’hydrogels d’acrylamide chargés en microgels encapsulant la R6G. Il a été trouvé que la libération des hydrogels chargés en microgels s’effectuait majoritairement selon l’affinité au microgel et sur une période d’environ 4-24 heures. La libération à partir de ces systèmes a été comparée à des formules d’hydrogels contenant des liposomes ou des nanogels de chitosan. Ces trois derniers (liposomes, microgels et nanogels) ont présenté des résultats prometteurs pour différentes applications avec différents profils de libérations. Enfin, nous avons transposé le modèle développé avec les gels d’acrylamide pour fabriquer des lentilles de contact de 260 à 340 µm d’épaisseur à base de pHEMA contenant les microgels avec une molécule encapsulée devant être administrée dans les yeux. Nous avons modifié la composition de l’hydrogel en incorporant un polymère linéaire, la polyvinylpyrrolidone (PVP). L’obtention d’hydrogels partiellement interpénétrés améliore la rétention d’eau dans les lentilles cornéennes. L’encapsulation dans les microgels chargés négativement a donné de meilleurs rendements avec la lidocaïne et cette dernière a été libérée de la lentille de pHEMA en totalité en approximativement 2 heures qu’elle soit ou non encapsulée dans des microgels. Ainsi dans cette étude pilote, l’impact des microgels n’a pas pu être déterminé et, de ce fait, nécessitera des études approfondies sur la structure et les propriétés de la lentille qui a été développée. En utilisant des modèles de libération plus représentatifs de la physiologie de l’œil, nous pourrions conclure avec plus de certitude concernant l’efficacité d’un tel système d’administration et s’il est possible de l’optimiser.

Transcultural satire in German fiction of Turkish migration: Self-deprecation, ethnic impersonation, intertexuality

My dissertation presents a study of satire in contemporary German Fiction of Turkish migration. Engaging with a body of works hitherto neglected in scholarship, I examine how satirical texts, films, and plays intervene critically in discourses on post-unification German national identity. Drawing on the seminal work of scholars such as Leslie Adelson, Tom Cheesman, B. Venkat Mani, Petra Fachinger, and Deniz Göktürk, my dissertation expands the scholarship of Turkish German Studies by linking a discussion of satire as a critical rhetoric to the question of how we talk about what it means to be German.

Chapter one offers a novel framework of the satirical vis-à-vis standard conceptions of satire and deconstructionist theories of reading. I understand satire as a form of rhetoric that creates moments of ambiguity by bringing together intersectional categories like gender, ethnicity, race, religion, in order to challenge the audience’s practices of interpreting cultural otherness. Chapter two examines the use of ethnic self-deprecation as one such strategy in Osman Engin’s short stories and his first novel, Kanaken-Ghandi through the lens of Bakhtinian polyphony and Judith Butler’s work on hate speech. Engin, I argue, employs ethnic selfdeprecation as a narrative strategy to straddle the line between deconstructing and re-affirming cultural stereotypes. Investigating the role of ethnic impersonation in Hussi Kutlucan’s film Ich Chef, Du Turnshuh, the third chapter turns to the question of ethnicity as a visual signifier for the negotiation of cultural inclusion and exclusion in post-1990 film. In dialogue with Katrin Sieg’s work on ethnic drag and Amy Robinson’s theory of passing, I show how the film challenges ethnically-coded narratives of Germanness. In the final chapter on Nurkan Erpulat and Jens Hillje’s play Verrücktes Blut, I discuss how intertextuality and adaptation (Hutcheon, Genette) of different story and character worlds are used to create moments of ambiguity and overdeterminacy in the play, in order to challenge the audience’s perception of what an inclusive German society might look like.

Pollen record from a swamp in Ukraine

(1967): In 1956-1962 investigations of swamps from the forest-steppe and steppe of Ukraine were carried out. They were followed by spore-pollen studies of swamp deposits. These materials are partially published in papers devoted to the history of vegetation in the south of Ukraine and re-vegetation of landscape in different phases of Holocene (Artyushenko, Bachurina, 1958; Artyushenko, 1959, 1960; Artyushenko, Kucheryava, 1964). Peat area in the investigated region is very small. In the forest-steppe peat occupies 1.1%, and in the steppe - 0.03% of the whole area (Peat Reserve of the Ukrainian SSR, 1959).

Las penas de encierro perpetuo desde una perspectiva histórica

Son pocos los trabajos publicados sobre la historia de las penas privativas de libertad, por lo cual llevo un tiempo dedicada a intentar llenar este vacío. En esta ocasión he querido explicar cuál ha sido el desarrollo de las sanciones de encierro perpetuo en los sucesivos Códigos Penales españoles, poniendo énfasis en el contexto político en el que se aprueban estos Códigos y las reformas de los mismos, así como también en las teorías de la pena y en las razones político-criminales que han contribuido a su justificación o crítica.

“Niemand zeugt für den Zeugen”. Temporalidad y memoria en la poesía de Paul Celan

El artículo analiza cómo Paul Celan, utilizando recursos arreferenciales y antimiméticos propios de la poésie pure y la poesía absoluta, desarrolla un modelo poético en el que la temporalidad y la memoria son determinantes. En el nuevo modelo, el lenguaje no constituye una realidad autónoma e inmanente; antes bien, se concreta en una acción dialógica y remite a una realidad extralingüística. El mismo texto poético configura un espacio del recuerdo, se erige en un lugar de memoria que, a través de las sedimentaciones históricas que arrastra el lenguaje, da testimonio de lo ocurrido.

La presencia del "flâneur" en "Tetralogie der Erinnerung" de Dieter Forte

Reflejando la ciudad moderna, el flâneur se encuentra atrapado entre dos tiempos: el presente, que se transforma continuamente, y el pasado, que permanece en forma de vestigios materiales. Desde su aparición en la literatura, la trayectoria del flâneur va ligada a los principales cambios históricos, sociales y culturales, que se plasman en distintas texturas urbanas. En todas ellas ejerce una función de nexo entre la ciudad antigua y la nueva que se superpone. El objeto del presente artículo es analizar la evolución de esta figura histórico y literaria como punto de partida para interpretar la obra en prosa Tetralogie der Erinnerung (1992-2004) de Dieter Forte.

La imagen de España en la novela de viaje "Cabo de Gata" de Eugen Ruge

Este artículo presenta un análisis de la imagen de España trazada en la novela Cabo de Gata (2013). Con ello se toma en consideración un género que, hasta ahora, ha recibido poca atención en la investigación de la imagen de España en la literatura de viajes alemana. El foco del análisis lo constituyen tanto el motivo del viaje como la percepción y representación de lo ajeno español. Por último, el análisis narratológico de los diversos aspectos seleccionados de la técnica narrativa nos servirá para delimitar la repercusión imagológica de la novela.

Analyzing Gene Centres with the Help of the Checklist Method – the Case of Syria

The present survey of species diversity of cultivated plants is the first for Syria. Some cultivated species will be added in the future, because due to the civil war in Syria, it was not possible to visit the country in the frame of the present work, as initially planned. Checklists proved to be a useful tool for overviewing the cultivated plants of selected areas and allow a characterization of the state of plant genetic resources of Syria. Syria has experienced several civilizations. Man settled in this productive land since ancient times and used its resources. However, such use has led to changes in vegetation and decline of wildlife through the country, in seashore areas, interior, mountains, and grassland. Plant domestication and growing started more than 10,000 years ago in West Asia. Since then, plentiful of economic plant species were present and used by man and his domesticated animals. Forming a part of the Fertile Crescent, where many of the world’s agricultural plants have evolved, Syria is extremely rich in agrobiodiversity. Wild progenitors of wheat and barley and wild relatives of many fruit trees such as almonds and pistachio as well as forage species are still found in marginal lands and less disturbed areas. These are threatened by a wide range of human activities, notably modern, extensive agriculture, overgrazing, overcutting and urban expansion. Syria is also considered as part of one of the main centres of origin, according to Vavilov, who had collected in Syria in 1926. The first expeditions to crop fields showed the exclusive nature of cultivated plants in Syria with a high number of endemic forms. Furthermore, Syria is a part of a biodiversity hotspot. Several studies have been performed to study agrobiodiversity in different parts of Syria, but usually on wild species. Many collections have been carried out; however, they focussed preferably on cereals and pulses, and particularly on wheat, like Vavilov’s expedition. Only 30 crops make up the major part of the conserved Syrian crop plant material in the genebank, indicating that most of the remaining 7,000 species of cultivated plants and many other valuable genetic resources species have only been included on a limited scale in the genebank collections. Although a small country (185,180 km2), Syria accommodates numerous ecosystems that allow for a large diversity of plant genetic resources for agriculture ranging from cold-requiring to subtropical crops to live and thrive. Only few references are available in this respect. The aim of the present study was to complete a checklist of Syria’s cultivated plants of agriculture and horticulture excluding plants only grown as ornamental or for forestry. Furthermore, plants taken for reforestation have not been included, if they do not have also agricultural or horticultural uses. Therefore, the inclusion of plants into the checklist follows the same principles as “Mansfeld’s Encyclopedia”. Main sources of information were published literature, floras of Syria, Lebanon and the Mediterranean, as well as Syrian printed sources in Arabic and/or English, reports from FAO on agricultural statistics in Syria, and data from ICARDA and Bioversity International. In addition, personal observations gathered during professional work in the General Commission for Scientific Agricultural Research (GCSAR) in Syria (since 1989) and participation in projects were taken into account. These were: (1) A project on “Conservation and Sustainable Use of Dry Land Agrobiodiversity in the Near East” with participation of Jordan, Lebanon, Syria, and the Palestinian Authority, focussing on landraces and wild relatives of barley, wheat, lentil, alliums, feed legumes, and fruit trees (1999–2005). (2) A project for vegetable landraces (1993–1995) in collaboration with the former International Plant Genetic Resources Institute and the UN Development Programme, in which 380 local vegetable accessions were evaluated. For medicinal plants and fruit trees I was in personal contact with departments of GCSAR and the Ministry of Agriculture and Agrarian Reform, as well as with private organizations. The resulting checklist was compared with the catalogues of crop plants of Italy and a checklist of cultivated plants of Iraq. The cultivated plant species are presented in alphabetical order according to their accepted scientific names. Each entry consists of a nomenclatural part, folk names, details of plant uses, the distribution in Syria (by provinces), a textual description, and references to literature. In total, 262 species belonging to 146 genera and 57 families were identified. Within-species (intraspecific) diversity is a significant measure of the biodiversity. Intraspecific diversity for wild plants has been and remains to be well studied, but for crop plants there are only few results. Mansfeld’s method is an actual logical contribution to such studies. Among the families, the following have the highest number of crop species: Leguminosae (34 spp.), Rosaceae (24), Gramineae (18), Labiatae (18), Compositae (14), Cruciferae (14), Cucurbitaceae (11), Rutaceae (10), Malvaceae (9), Alliaceae (7), and Anacardiaceae (7). The establishment of an effective programme for the maintenance of plant genetic resources in Syria started in the mid-1970s. This programme considered ex situ and in situ collection of the genetic resources of various field crops, fruit trees and vegetables. From a plant genetic resources viewpoint, it is clear that the homegarden is an important location for the cultivation of so-called neglected and underutilized species (neglected from a research side and underutilized from a larger economic side). Such species have so far not received much care from ecologists, botanists and agronomists, and they are considerably under-represented in genebanks.

Möbel mit Persönlichkeit (Personalisierbare Möbel) : Entwurfsansätze für individualisierbare Möbelstücke

In unserer heutigen Wegwerfgesellschaft ist alles schnell und kurzlebig geworden. Wir wachsen mit dem Wissen auf, dass nichts für immer hält. Meistens gehen Dinge kurz nach Ablauf der Garantie kaputt, ein neure Trend entsteht, es ist einfach nicht mehr schick genug oder man zieht um und das damals gekaufte passt nicht mehr zu der neuen Einrichtung. Es gibt viele Gründe warum das Möbelstück schnell gegen ein moderneres und praktischeres ausgetauscht wird. In unserer Gesellschaft ist es nicht wichtig Möbel lange zu behalten, es gibt ja genug Auswahl und immer etwas Neues das ist der Knackpunt. Wie bekommt man jemanden dazu. Dass er seine Möbel mehr Wert schätzt? Wie kann der Nutzer eine dauerhafte Bindung zu seinem Möbelstück erhalten? So, dass es eben nicht in der nächsten Saison aussortiert wird?Dieses Thema setzte ich anhand der Research (128 Seiten Format: 210mm x 190mm) und der Dokumentation (64 Seiten Format: DIN A4) um.