The paper aims to mediate thin film chromatography analysis by means of drugs commonly found in households (analgesic-antipyretics) to secondary school and grammar students, or to college students. For this purpose, laboratory tasks have been designed to cover all levels of the Bloom pyramid so that the educational potential is as high as possible. This is closely related to the topic of drug expiration and treatment. Pupils and students should take on both the competences of knowledge, skills, and attitudes. Keywords: thin layer chromatography; TLC; chromatography in education; educational experiment; expiratory medication; drug handling; analgesic- antipyretics, acetylsalicylic acid, paracetamol

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Eliška Holinská Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Pharmacoteraphy of headache in adults Headache is one of the most common health problem that encounters almost everyone during the life. Depending on the cause, headaches can be divided on the primary headaches, which are the subject of the diploma thesis, and secondary headaches, which are caused by other diseases. The primary headaches are migraine, tension-type headache, cluster headache and primary chronic daily headache. Headache is not a life-threating condition but it can significantly reduce the quality of life, particularly the chronic forms of headache. The determination of the right diagnosis is essential for the choice of appropriate therapy. For primary headache are typical negative test results, there are no structural lesions or signs of organic brain damage. Diagnostics is comlicated and it is primarily based on a carefully processed medical history. In the therapy of primary headache are used both pharmacological and non-pharmacological methods, optimaly in combination. Pharmacological treatment consists of preventive and acute therapy. The preventive treatment is given to reduce the...

To determine the ecotoxicity of analgetics, first the individual ecotoxicity values of individual analgetics are determined and then a mixture of two analgetics is tested. To determine the toxicity, both standard and alternative toxicity tests are used (daphnia magna, sinapsis alba, scenedesmus subspicatum, vibrio fischeri, thamnotoxkit FTM a daphnotoxkit FTM magna). The analgetics being whish tested are the commonly used medicines ibuprofen, ASA, diclofenac and paracetamol, which are the most frequently used medicines in the Czech Republic and whole Europe. To determine the ecotoxicity of the polymers, I‘m using an indirect method of examination, in which I determine the antagonistic or synergistic effects of the mixture of monomers from which the polymer is prepared and into which it slowly decomposes in nature. For the determination both standard and alternative toxicity tests are used. The polymers the toxicity of which is being determined are the habitually used polymer PET and the formaldehyde resine known as bakelite in Eastern Europe.

(EN) In the first part of this work, analytical methods for determination of impurities of active pharmaceutical ingredients (API) in combined pharmaceutical dosage forms were developed and validated. Development of the methods covered both the optimization of sample preparation procedure and chromatographic conditions. The methods were validated according to International Conference on Harmonization guideline and both of them were confirmed to be able to analyze stability samples. Impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fourth API fenpiverinium bromide were separated by using ion-pair reversed phase chromatography with gradient elution. Symmetry C18, 250 x 4,6 mm, 5 µm heated to 35 řC was used as a separation column. A diode array detector was used. The detection wavelengths were set as follows: 220 nm for paracetamol impurity K, 245 nm for paracetamol and its other impurities and 285 nm for codeine, pitophenone and their impurities. Impurities in valsartan, amlodipine besylate and hydrochlorothiazide were separated by reversed phase UHPLC method with gradient elution. Chromatographic column Zorbax Eclipse C8 RRHD, 100 x 3,0 mm, 1,8 µm heated to 30 řC and spectrophotometric detection were used. The detection wavelengths were set as...

Ce travail étudie la faisabilité de différents procédés d’oxydation avancée (POAs) pour le traitement d’eaux usées industrielles. Le secteur visé est l’industrie pharmaceutique, les essais ont été menés sur des eaux synthétiques contenant deux molécules modèles: le paracétamol et la ciprofloxacine. Les procédés étudiés dans ce travail sont l’ozonation, la sonochimie, le traitement par radiation gamma et la dégradation par radiation ultraviolet. Ces techniques sont envisagées en mono-traitement ou en combinaison avec des oxydants et/ou des catalyseurs (peroxyde d’hydrogène, réactif de Fenton et zéolite Fe/MFI). Pour chaque procédé, l'influence de différents paramètres opératoires est analysée et interprétée dans l'objectif de déterminer les meilleures conditions pour la conversion et la minéralisation du chaque polluant. Parmi les paramètres étudiés se trouvent le pH, la concentration en oxydant, la concentration du catalyseur, la dose de la radiation gamma, la fréquence et la puissance ultrasonore. Des effets synergiques importants sont trouvés pour l’ozonation catalytique et pour le photo-Fenton par rapport aux procédés seuls. D’un point de vue purement énergétique, les traitements les plus efficaces sont l’oxydation radio- Fenton et l’oxydation photo-Fenton. Sur la base de ces résultats, un photo-réacteur solaire à recirculation est mis en oeuvre pour traiter par oxydation photo-Fenton des solutions synthétiques préparées avec un mélange de paracétamol et de ciprofloxacine dans l’eau du robinet mais aussi avec des eaux usées réelles dopées avec les deux composés. Dans les deux cas, la dégradation des molécules dépasse 95% dans les 15 premières minutes et la minéralisation dépasse 55% en 180 minutes. / In this work, the feasibility of paracetamol and ciprofloxacin degradation by different advanced oxidation processes (AOPs) was investigated. These molecules are representative of pharmaceutical pollutants found in wastewater. The used processes were the ozonation, the high frequency ultrasound, the gamma radiation and the ultraviolet radiation, alone or in combination with oxidizers and/or catalysts (hydrogen peroxide, Fenton’s reagent and zeolite Fe/MFI). The influence of different operations parameters (pH, oxidant concentration, catalyst concentration, gamma radiation dose and ultrasonic power and frequency) for each processes were studied, in order to determine the optimal operating ranges for the degradation and mineralization of the pharmaceuticals pollutants. Results showed marked synergistic effects by combining individual processes with hydrogen peroxide or Fenton’s reagent, being the most important synergy factors those corresponding to the heterogeneous catalytic ozonation and photo-Fenton processes. Taking into account the energy consumption, the mineralization and the synergy factor, the most effective treatments were radio-Fenton oxidation and photo-Fenton oxidation. Optimal conditions for photo-Fenton oxidation were studied in an open channel reactor at bench scale in tap water and in a real matrix from a municipal wastewater treatment plant. Samples were spiked with a mixture of the pharmaceuticals. In both cases 95% degradation within the first 15 minutes was achieved and its mineralization exceeded 55% in three hours.

This work entails efforts to understand effects of solvent choice on paracetamol crystallization. Various techniques have been developed and implemented to study aforementioned. A clear-cut, direct evidence of two-step nucleation mechanism is demonstrated using a bench top Raman spectrometer and a novel method named as OSANO. / Polymorphismus ist die Eigenschaft vieler anorganischer und insbesondere organischer Moleküle, in mehr als einer Struktur zu kristallisieren. Es ist wichtig, die Faktoren zu verstehen, die den Polymorphismus beeinflussen, da er viele physikochemische Eigenschaften wie Stabilität und Löslichkeit beeinflusst. Nahezu 80 % der vermarkteten Medikamente weisen Polymorphismus auf. In dieser Arbeit wurde der Einfluss der Wahl des organischen Lösungsmittels auf den Polymorphismus von Paracetamol untersucht und verschiedene Methoden entwickelt und angewandt, um den Einfluss genauer zu verstehen. Es wurde festgestellt, dass Ethanol viel stärker auf Paracetamol-Kristallisation als Methanol wirkt. Nichtgleichgewichts-Molekulardynamiksimulationen mit periodischer, simulierter Abkühlung (Simulated Annealing) wurden verwendet, um Vorläufer der metastabilen Zwischenprodukte im Kristallisationsprozess zu untersuchen. Es wurde festgestellt, dass die Strukturen der Bausteine der Paracetamol-Kristalle durch geometrische Wechselwirkungen zwischen Lösungsmittel und Paracetamol bestimmt werden. Die statistisch häufigsten Bausteine in der Selbstassemblierung definieren die finale Kristallstruktur. Ein speziell angefertigter akustischer Levitator hat die Proben zuverlässig gehalten, wodurch die Untersuchung des Einflusses von Lösungsmitteln ermöglicht, heterogene Keimbildung abgeschwächt und andere Umgebungsfaktoren stabilisiert wurden. Die Kristallisation wurde in diesem Aufbau mit zeitaufgelöster In-situ-Raman-Spektroskopie verfolgt und mit einer neuen Zielfunktion basierenden Methode der nichtnegativen Matrixfaktorisierung (NMF) analysiert. Orthogonale Zeitrafferfotografie wurde in Verbindung mit NMF verwendet, um eindeutige und genaue Faktoren zu erhalten, die sich auf die Spektren und Konzentrationen verschiedener Anteile der Paracetamol-Kristallisation beziehen, die als latente Komponenten in den unbehandelten Daten vorhanden sind. / Polymorphism is the property exhibited by many inorganic and organic molecules to crystallize in more than one crystal structure. There is a strong need for understanding the influencing factors on polymorphism, as it is responsible for differences in many physicochemical properties such as stability and solubility. Nearly 80 % of marketed drugs exhibit polymorphism. In this work, we took the model system of paracetamol to investigate the influence of solvent choice on its polymorphism. Different methods were developed and employed to understand the influence of small organic solvents on the crystallization of paracetamol. Non-equilibrium molecular dynamics simulations with periodic simulated annealing were used as a tool to probe the nature of precursors of the metastable intermediates occurring in the crystallization process. Using this method, it was found that the structures of the building blocks of crystals of paracetamol is governed by solvent-solute interactions. In situ Raman spectroscopy was used with a custom-made acoustic levitator to follow crystallization. This set-up is a reliable method for investigating solvent influence, attenuating heterogeneous nucleation and stabilizing other environmental factors. It was established that as a solvent, ethanol is much stronger than methanol in its effect of driving paracetamol solutions to their crystal form. The time-resolved Raman spectroscopy crystallization data was processed using a newly developed objective function based non-negative matrix factorization method (NMF). An orthogonal time-lapse photography was used in conjunction with NMF to get unique and accurate factors that pertain to the spectra and concentrations of different moieties of paracetamol crystallization existing as latent components in the untreated data.