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Relative Bio-Equivalence of Salbutamol MDIs Without and With the Attached Spacers. Development and validation of novel HPLC methods for the determination of salbutamol (and terbutaline) in urine excreted post-inhalation for bioequivalence and pharmacokinetic studies of Salbutamol MDIsMazhar, Syed H.R. January 2018 (has links)
This research explored in-vitro and in-vivo performance of three salbutamol metered dose inhalers (MDIs): Ventolin Evohaler (Evo), Airomir (Airo) and Salamol. In the in-vitro studies, critical quality attributes of the MDI using an Andersen cascade impactor (ACI) were examined and included measurement of fine particle dose (FPD) and total delivered dose (TDD). Bioequivalence studies were conducted in humans using the urinary pharmacokinetic method. Post-inhalation urinary excretion of salbutamol in the first 0.5 hour (lung deposition, USAL0.5) and over 24 hours (total systemic bioavailability, USAL24) were compared to determine the bioequivalence of the MDIs. The spacers recommended for use with these inhalers were also studied, and charcoal block studies were performed to assess the extent of USAL0.5.
The three MDIs had FPD (μg) of 78, 91 and 89, respectively; the latter pair was equivalent. Their USAL0.5 (6, 7 & 7 μg) was however not bioequivalent. These MDIs delivered equivalent dose (177, 174 & 180 μg) which reflected on their USAL24 (101, 84 & 97 μg). Nevertheless, USAL24 was inequivalent between Evo and Airo.
The FPD of Evo with Volumatic (VOL), AeroChamber Plus (AERO) and Able spacer was 78, 68 and 74 μg, respectively. The AERO treatment method was not equivalent to the MDI while VOL and Able were equivalent between them. Spacer USAL0.5 (16, 15 & 14 μg) was not bioequivalent to the MDI but to each other. The spacer in-vitro TDD (95, 85 & 92 μg) was inequivalent to the MDI treatment method. In contrast, their USAL24 was bioequivalent (97, 85 & 90 μg).
The FPD of Airomir with AERO (95 μg) was in-vitro equivalent while USAL0.5 (15 μg) of this treatment method was bio-inequivalent to the MDI alone. On the contrary, the TDD (110 μg) and USAL24 (84 μg) of AERO were respectively in-vitro inequivalent and bioequivalent to the MDI alone.
The FPD (μg) of Salamol MDI alone and with VOL (84) and AERO (86) as well as between the spacers was equivalent. However, the USAL0.5 of the MDI was not bioequivalent to spacers (20 and 18 μg) despite being equivalent between the spacers. In contrast, the respective TDD (103 and 95 μg) of spacer treatment methods were in-vitro inequivalent to the MDI alone albeit having bioequivalent USAL24 (86 and 87 μg).
The variations in the in-vitro performance of the three MDIs are most likely due to differences in their formulations and designs. As the performance metrics of the MDI influence lung deposition, substituting one MDI with another can have clinical implications.
Although the spacers reduced in-vitro TDD of the MDI to about half, their use increased lung deposition by over two folds, the magnitude of which varied with the MDI and spacer type. Despite significant decrease in dose delivery, the total systemic bioavailability with the spacers was similar to that with the MDI alone. This systemic bioequivalence is more likely due to greater USAL0.5 with the spacers. The results of the charcoal block studies reinforced this outcome.
The present study is unique as it used a clinically relevant salbutamol MDI dose (two puffs), assessed results for equivalence and analysed ACI deposition data further as stage groups. The deposition on adjacent ACI stages were grouped together as coarse, fine and extra-fine particle masses to identify their more likely deposition sites in the human respiratory tract. Moreover, this thesis describes highly sensitive and novel HPLC and SPE methods, developed and validated to quantify salbutamol in urinary and aqueous matrices.
As the clinical effects of MDIs are related to their lung deposition, the current work emphasizes the importance of spacer use. Nevertheless, differences in dose delivery between spacers may have clinical consequences. Hence, only the specific spacer recommended for use with the MDI should be used. / World Federation, Stanmore, London and Sadaat Welfare Foundation, Bradford, West Yorkshire
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Fracture strength of three-unit fixed partial denture in lithium disilicate, press versus milled, in-vitro studyIsmail Ahmad, Hogir, Khazal, Noor January 2019 (has links)
Syfte: Syftet med denna studie är att jämföra fraktur styrkan och frakturmönster hos tre-leds broar utförda i litiumdisilikat när broarna tillverkas genom pressteknik jämfört med frästa tre-leds broar genom CAD/CAM system.Hypotes: Pressteknik är bättre lämpad med avseende till fraktur resistens då fräsning av litiumdisilikat block kan resultera i defekter och spänning i materialet, detta gör materialet mer benäget till chipping/mikroabrasioner på ytan som skulle kunna propagera och på så sätt påverka fraktur resistensen. P-värde sattes till p ≤0.05.Material och metod: 40 3-leds broar tillverkades med pressteknik jämfört med fräst teknik med CAD/CAM system i grupper. Dessa delades in i undergrupper baserat på anatomin. Broarna genomgick en artificiell åldringsprocess som utgjordes av termocykling och förbelastning. Efter den artificiella åldringsprocessen utsattes broarna för belastning fram till fraktur. Den statistiska datan samlades in och analyserades. Även fraktur mönstret analyserades. Resultat: Där fanns ingen signifikant skillnad gällande fraktur styrkan mellan de full anatomiska grupperna. Där fanns inte heller någon signifikant skillnad gällande fraktur styrkan mellan underkonstruktion grupperna. Hypotesen falsifieras därför.Slutsats: Där fanns ingen signifikant skillnad gällande hur mycket belastning det krävs för att frakturera broarna som tillverkats genom pressteknik jämfört med broarna tillverkade med hjälp av CAD/CAM teknik. Där finns ett tydligt mönster gällande fraktur mönstret men en slutsats kan inte dras med tanke på antalet broar som använts. / Aim: The aim of this study was to compare fracture load and fracture mode of three-unit fixed partial dentures, made in lithium disilicate when the FDPs are made with pressing technique versus milled with a CAD/CAM system.Hypothesis: Pressing technique is better suited with regards to fracture load since milling of lithium disilicate blocks can result in defects and tension build up in the material, leaving the material more prone to chipping/micro-abrasions on the surface that could propagate and thus affecting the fracture load. P-value set to p ≤0.05.Material and methods: 40 FDPs where manufactured with pressing technique versus milled with a CAD/CAM system in each group. Furthermore, each group where subdivided depending on the anatomy. The FDPs thereafter underwent an artificial ageing process consisting of thermocycling and preloading. After the artificial aging process the FDPs were subjected to load to fracture, where the statistical data was collected and analyzed. Also, the fracture mode was observed and analyzed.Results: There was no significant difference regarding the fracture strength between the full anatomy groups. There was also no significant difference regarding the fracture strength between the core-design groups. The hypothesis was therefore rejected.Conclusion: There is no significant difference with regards to how much load is required to fracture FDPs made through pressing technique compared to FDPs made through the use of CAD/CAM technique. There is a clear pattern regarding the fracture patterns, however a conclusion can’t be drawn considering the sample size.
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Filosofie pro děti v programu dalšího vzdělávání pedagogických pracovníků / Philosophy for Children in Teacher Training ProgramsKOZUBÍKOVÁ, Iva January 2008 (has links)
Diplomová práce se zabývá rámcově vzdělávacími programy v předškolním a základním vzdělání a jaký mají vliv na dítě v době výchovně {--} vzdělávacího procesu. Také pedagogickými pracovníky, kteří se zasluhují velkou měrou o tento proces, hlavní zaměření je na pracovníky ve volnočasové sféře. Je zde zahrnut dialog jako podporující faktor pro kvalitnější vyučování a nejen to, je brán jako výborná forma komunikace mezi žákem a jeho pedagogem. Současně s tím zde uvádím důležitou pomůcku pro vzájemný dialog Filozofii pro děti a s tím i jaký má smysl a význam pro obě výše uvedené strany. Své úsudky opírám o vlastní zkušenost z intenzivních seminářů na Teologické fakultě v Českých Budějovicích. V závěru diplomové práce jsou informace o programu DVPP, který má napomoci učitelům a pedagogickým pracovníkům systematicky posilovat své odborné kompetence, a tak být určitou zárukou jejich určitou zárukou jejich odborné kvalifikace po celou dobu profesní kariéry. Je zde i uvedena Koncepce dalšího vzdělávání pedagogických pracovníků školských zařízení pro zájmové vzdělávání a odborné přípravy pracovníků s dětmi a mládeží v oblasti volného času, která by měla být nápomocnou pro jednodušší a více oborově zaměřenou nových vzdělávacích programů jako je například Filozofie pro děti.
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