Comparative bioavailability of two oral formulations of clopidogrel: Determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects

Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka’s formulation to the innovator’s formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations

Reflection on the Soča River in a glass sculpture

V diplomski nalogi je opisano moje doživljanje reke Soče ob obisku doline Trente in odkrivanje njene okolice. Gre za črpanje inspiracije iz narave, iskanje utemeljitve ob literarni opori ter opis procesa izdelave steklene skulpture. Analitično-raziskovalni del diplomske naloge mi bo služil kot izhodišče za nadaljnje delo, pri raziskovanju in boljšem spoznavanju in povezovanju reke Soče, vode, svetlobe in skulpture. Vse bom skušala strniti v premišljen koncept, ki bo temeljil na izboru vsebin, ki si smiselno sledijo v tematskem zaporedju. V poglavjih bom večjo pozornost namenila razvoju in raziskavi tistih likovnih vprašanj, ki mi bodo v pomoč pri razvijanju, načrtovanju in nastajanju steklene skulpture.This thesis describes my experience of the river Soča on the occasion of my visit of Trenta valley and exploration of its surroundings. I drew inspiration from nature, sought support in literature and described the process of producing a glass sculpture. Analytical and research part of my thesis will serve as the basis for further research in understanding and connecting with the river Soča, water, light, and the sculpture. I will attempt to piece everything together into a well-thought-out concept, based a selection of content, in a logical sequence. In the following chapters, I will pay more focus on development and research of those fine art issues that will aid me in the development, planning and making of a glass sculpture

THE STRUCTURE OF HANDBALL TRAINING PLAN PREPARATION / PROCESS

Načrtovanje vadbenega procesa pri rokometu je zelo zahtevno in kompleksno, saj zahteva ogromno znanja in izkušenj. Proces se sooča s številnimi dejavniki, ki ga opredeljujejo in spreminjajo. Za dobro načrtovanje je treba poznati ključne elemente in procese športne vadbe ter ciklizacije. Kakovosten vadbeni proces je rezultat pravilnega načrtovanja, izbire različnih oblik športne vadbe in metod, s katerimi bomo izboljšali posamezne motorične sposobnosti rokometašev do takšnega ravni, ki je samo z rokometno igro ne moremo doseči. Rokomet je kompleksen šport, pri katerem je potreben razvoj vseh motoričnih sposobnosti, kajti le tako so rokometaši sposobni reševati tehnično-taktične probleme med tekmo v najkrajšem možnem času, s čimer prispevajo tudi k večji dinamičnosti same igre. V diplomskem delu smo se osredotočili na razvoj gibalnih in funkcionalnih sposobnosti, s katerimi vplivamo na boljšo telesno pripravljenost rokometašev ter prav tako preventivno vplivamo na možnost nastanka poškodb. S pomočjo domače in tuje strokovne literature smo razčlenili vsako motorično sposobnost in teoretično opisali sredstva in metode, s katerimi jih lahko na treningih razvijamo. Prav tako smo opisali in podali praktične primere sestave treningov za razvoj posameznih motoričnih sposobnosti, ki so pomembni za rokometno igro. Namen dela je teoretično in praktično predstaviti celoten vadbeni proces rokometašev ter s tem prispevati k večjemu zavedanju pomena pravilnega načrtovanja priprav in treningov tako trenerjev kot tudi igralcev. Delo bo koristilo trenerjem rokometa na vseh tekmovalnih stopnjah.The structure of handball training process is very complicated because it involves selecting objectives, knowledge and experiences. Planning is a process of thinking in advance what is had to be done and how. It is an anticipatory decision making. It involves selecting objectives and developing action programs for achieving them. Success becomes a matter of planning rather than physical and psychological challenges, this is because plans are predetermined course of actions. Planning has an effective meaning ensuring continuous personality development and improving athletic performance and enabling athletes of top-class age to achieve the highest standard of performance. By choosing different sport exercises and using different training methods, particular motor skills can be improved to the level, which could not be reached only by playing handball. Quality and professional conditioning drill forms are the basis of every handball training. Only the most physically prepared handball players are able to play at high level. Since handball is a complex sport, it is important for the handball players to develope motor skills. Only then, they are able to quickly cope with all the technical and tactical problems during the match, which makes it more dynamic. This diploma thesis focuses on the developement of motor and functional skills, which are important for the handball players to get in the best form and to avoid injuries. On the basis of domestic and foreign literature, every motor skill was analysed. Moreover, means and methods as well as exercises to develope all the motor skills needed were described. The purpose of the diploma thesis is to present how to do a plan, how we structure a handball process for handball players not only in theory but also in practice. In this way, the handball coaches as well as the handball players would become more aware of the importance of the conditioning drill and of improving motor skills. The diploma thesis will be a great help to every handball coach

(Pre)oblikovanje organizacijske kulture

Orgnizacijska kultura je proizvod skupinske izkušnje in jo zato lahko najdemo samo tam, kjer obstoji definirana skupina s pomembno zgodovino. Bistvo organizacijske kulture je skupna vednost, ki se oblikuje v procesu razvoja organizacije (še zlasti skozi dogodke, ki jih za nazaj lahko označimo kot kritične) in predstavlja referenčno shemo za razlago sveta in delovanje v njem. Potrebno jo je sprememniti, ko postane disfunkcionalna za delovanje organizacije, saj je njena glavna vloga reševanje problemov prilagajanja in preživetja v (spreminjajočem) okolju, ter notranja integracija. Načrtne spremembe organizacijske kulture niso vedno mogoče, njihova podlaga pa je v vzajemnem spreminjanju sociostrukturnega sistema organizacije in v komuniciranju novih stališč in vrednot članom organizacije

Development and analysis of novel polymeric coatings with integrated pharmaceutical substances on titanium/aluminium/vanadium alloy

V diplomskem delu je predstavljena zasnova in analiza novih polimernih oblog, ki imajo vgrajene zdravilne učinkovine na zlitini Ti90/Al6/V4. Namen zasnove polimernih oblog je njihova potencialna uporaba v ortopedske (protetični implantanti – kolena, umetni kolki, ipd.) in zobozdravstvene namene. S pomočjo študije oblaganja vzorcev, karakterizacije tankih filmov in testiranja in vitro sproščanja, želimo spoznati možnost uporabe te zlitine v otropedski medicini, kjer bi se zdravilna učinkovina sproščala neposredno na določeno mesto in tako zagotovila ciljano sproščanje te učinkovine, prav tako pa bi bolniku pomagala pri okrevanju po operativnem posegu. Vgrajena zdravilna učinkovina sodi v skupino nesteroidnih protivnetnih učinkovin (NSAID). Rezultati študije karakterizacije vzorcev so pokazali prisotnost dveh glavnih komponent, to sta diklofenak in mešanica polimerov, kar smo potrdili s karakterizacijo tankih filmov z ATR-FTIR metodo, rezultati in vitro sproščanja pa so potrdili, da sproščanje zdravilne učinkovine vselej poteka po istem mehanizmu, in sicer v treh stopnjah: zelo hitro, hitro in zelo počasno sproščanje. Pritrdimo lahko, da se največ zdravilne učinkovine sprosti v prvih 360 minutah, kar prispeva k ciljanem odmerjanju le-te.This bachelor thesis presents the design and analysis of new polymer coatings with integrated active substances on Ti90/Al6/V4 alloy. These polymer coatings have the potential for being used in orthopedic (prosthetic implants – artificial hips, knees, elbows, etc.) and dental purposes. With the help of case study on coating substrates, characterisation of thin films and testing in vitro release, we want to determine whether it is possible to use such materials in orthopedic medicine, where the active substance would be released directly onto specified location and thus ensure a targeted release of the substance and further also help a patient recover after surgical procedure. Integrated active substance belongs to the group of nonsteroidal anti-inflammatory drugs (NSAID). Results of the study on characterization of thin films showed presence of two main components: diclofenac and a mixture of polymers, which were confirmed with the characterization of thin films by ATR-FTIR method. The results of in vitro release state that the release of the active substance always takes place in the same mechanism in three stages: very fast release, fast release and very slow release. In conclusion, most of the active substance releases in the first 360 minutes, which contributes to targeted dosing

A cat-litter box

Pri inovaciji mačjega stranišča sem se osredotočila na problematiko kompleksnosti uporabe z vidika mačke in človeka kot uporabnika, s poudarkom na boljši funkcionalnosti ter izboljšanju vizualne podobe. V nalogi sem se osredotočila na notranje mačke in njihove potrebe ob uporabi stranišča. Največ problemov sem zaznala kot posredni uporabnik in jih upoštevala kot izhodišče za mojo rešitev z namenom olajšanja postopka uporabe. Raziskala sem obstoječe rešitve na trgu in želela brez vključevanja tehnologije v končni izdelek razviti enostavno za uporabo, cenovno ugodno in oblikovno zanimivo rešitev. Pri tem sem upoštevala umestitev samega elementa v prostor, ki bo funkcioniral tudi kot samostojen pohištveni element v domačem okolju.When innovating cat litter box, I focused on the complexity of use from the viewpoint of both cat and human, with the stress on improved practicality and image. In my thesis I focused on indoor cats and their toilet needs. I noticed most problems as an indirect user and have used those problems as a starting point for my solution with the aim of simplifying the litter box’s usage. I researched existing solutions on the market and wanted to develop an easy-to-use and cheap solution with an attractive design, without integrating technology into finished product. At the same time I considered design of the product which will function as an independent piece of furniture at home

Application of deep eutectic solvents as a green alternative for extraction of active substances from milk thistle (silybum marianum)

Magistrsko delo prikazuje študijo priprave globoko evtektičnih topil kot nadomestnega medija škodljivim organskim topilom za ekstrakcijo aktivnih učinkovin iz pegastega badlja. V okviru magistrske naloge smo pripravili pet globoko evtektičnih topil različne sestave ter dodatno 80 % etanol kot konvencionalno organsko topilo in preverjali, katero od njih je najbolj ugodno za ekstrakcijo silimarinov iz pegastega badlja. Za sintezo globoko evtektičnih topil smo uporabili naslednje spojine: holin klorid, mentol, 1,4-butandiol, 1,2-propandiol, mlečno kislino in sečnino. Po HPLC analizi smo iz kromatogramov in enačbe umeritvene premice izračunali, kolikšna je bila koncentracija skupnih silimarinov, ki smo jih ekstrahirali iz posameznega vzorca. Vsa DES topila, razen DES2 (mentol : 1,4-butandiol v razmerju 1 : 2), so bila redčena z vodo, in sicer v razmerju 75 % DES-25 % H2O. Ugotovili smo, da se je največ silimarinov sprostilo v 80 % etanolu, ki je polarno protično topilo. Sledili sta globoko evtektični topili iz holin klorida in 1,2-propandiola ter holin klorida in 1,4-butandiola. Njima sta sledili globoko evtektični topili iz holin klorida in mlečne kisline ter holin klorida in uree (sečnine), najmanj silimarinov pa se je sprostilo v globoko evtektično topilo iz mentola in 1,4-butandiola, ki je bilo tudi edino topilo, ki ni vsebovalo vode, torej hidrofobno. Iz rezultatov je razvidno, da je prisotnost vode v topilu pozitivno vplivala na izkoristek ekstrakcije silimarinov iz pegastega badlja, vendar so bile koncentracije skupnih silimarinov, ekstrahiranih iz pegastega badlja, kljub temu izredno nizke, zaradi česar bo v prihodnje potrebnih še veliko raziskav, da bi to lahko izboljšali.This masters thesis presents a study of the preparation of deep eutectic solvents as a substitute medium for harmful organic solvents during the extraction of active substances from milk thistle. As part of this thesis, we prepared five deep eutectic solvents and an additional solvent of 80 % ethanol and studied which is more suitable for the extraction of silymarins from milk thistle. The following compounds were used for synthesis of the deep eutectic solvents: choline chloride, menthol, 1.4-butanediol, 1.2-propanediol, lactic acid and urea. After HPLC analysis, the concentration of total silymarins extracted from each sample was calculated using the chromatograms and the calibration line equation. All deep eutectic solvents except DES2 (menthol : 1.4-butanediol in a ratio of 1 : 2) were diluted with water in a ratio of 75 % DES to 25 % H2O. We determined that the 80 % ethanol, which is a polar protic solvent, released the most silymarins. This was followed by deep eutectic solvents made of choline chloride with 1.2-propanediol and then choline chloride with 1.4-butanediol. Those were followed by deep eutectic solvents combining choline chloride with lactic acid and choline chloride with urea. The fewest silymarins were released into the deep eutectic solvent made of menthol and 1.4-butanediol, which was also the only used hydrophobic solvent. The results show that the presence of water in the solvent had a positive effect on the efficiency of silymarin extraction from milk thistle. However, concentrations of total silymarins extracted from the milk thistle using all solvents remained extremely low. Further research will be required to improve upon these results