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Vrednotenje vpliva simulacije luminalnih pogojev želodca na gelsko plast ogrodnih tablet
Kreft, Klemen (Author), Trontelj, Jurij (Mentor) More about this mentor... This link opens in a new window, Legen, Igor (Co-mentor)

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Abstract
Posnemanje in vivo pogojev z metodami in vitro omogoča različno dobro približanje fiziološkim pogojem. Znana je biorelevantna naprava za posnemanje želodčnega gibanja, ki so jo razvili v podjetju Lek d.d. v Ljubljani v sodelovanju s Fakulteto za strojništvo iz Univerze v Ljubljani. Naprava za posnemanje želodčnega gibanja boljše posnema in vivo pogoje zaradi anatomske podobnosti človeškim želodcem, sposobnosti posnemanja krčenja želodčne stene, prožne silikonske vreče in posnemanja migracijskega motoričnega kompleksa, ki se pojavi na tešče. S tem se naprava bistveno razlikuje v delovanju glede na konvencionalno napravo za sproščanje z vesli. Glavni namen magistrske naloge je bil ovrednotiti mehanski vpliv naprave za posnemanje želodčnega gibanja na hidrofilne ogrodne tablete ter raziskati vpliv prehoda tablete skozi želodec in kako to vpliva na kinetiko sproščanja. Preučili smo tudi vpliv biorelevantne umetne želodčne tekočine, ki posnema želodčne pogoje na tešče, v primerjavi z 0,01 M HCl z ioni v obeh napravah. V prvem sklopu magistrske naloge smo z napravo za vrednotenje teksture na dveh serijah tablet z različno sestavo izmerili manjšo debelino gela po nabrekanju v napravi za posnemanje želodčnega gibanja kot v napravi z vesli. Naprava za posnemanje želodčnega gibanja izvaja močne mehanske in (predvidoma tudi) hidrodinamske sile neposredno na površino nabreklih vzorcev. Odstranjevanje vrhnjih plasti gelskega sloja je zato izrazitejše, erozija gela je prav tako večja kot v napravi z vesli. Na debelino in erozijo gela izbira biorelevantnega medija nima bistvenega vpliva. V drugem sklopu magistrske naloge smo preučevali vpliv mehanskih sil naprav za posnemanje želodčnega in intestinalnega gibanja na sproščanje dipiridamola na novi seriji tablet. Razmeroma dobro smo posnemali tlačne pogoje v lumnu želodca in tankega črevesa in vivo. Tega z uporabo naprave z vesli ni mogoče doseči. Prav zato je v sklopu naprav za posnemanje želodčnega in intestinalnega gibanja kinetika sproščanja dipiridamola hitrejša, celokupno sproščanje pa obsežnejše kot v napravi z vesli. Nadalje smo s pomočjo kompleksne kriostatske metode določili pH gradient znotraj gelske plasti formulacije v obeh napravah. Naši rezultati so pokazali značilne razlike v procesih sproščanja farmacevtskih oblik v klasičnih in biorelevantnih napravah. Te razlike smo tudi uspešno razložili z uporabo naprednih analiznih tehnologij, kot sta ploskovno merjenje pH in analiza teksture ter mehanskih lastnosti nastalega hidrogela.

Language:Slovenian
Keywords:naprava za posnemanje želodčnega gibanja, naprava za vrednotenje teksture, hidrofilne ogrodne tablete, mehanska obremenitev, pH gradient
Work type:Master's thesis/paper (mb22)
Organization:FFA - Faculty of Pharmacy
Year:2019
Views:122
Downloads:41
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Secondary language

Language:English
Title:Evaluation of the simulated stomach's luminal environment influences on the gel layer of the matrix tablets
Abstract:
Simulating in vivo conditions using in vitro methods allows for a fairly good approximation of physiological conditions. One of the in vitro biorelevant devices is the advanced gastric simulator, which was developed at Lek d.d. in Ljubljana in cooperation with the Faculty of Mechanical Engineering, University of Ljubljana. Advanced gastric simulator imitates in vivo conditions due to anatomical similarities to human stomach, ability to mimic gastric wall contraction, flexible silicone container and migrating motor complex simulation, which occurs in fasting conditions. In this way, it significantly differentiates in performance with respect to the paddle dissolution apparatus. The aim of this master's thesis was to evaluate the mechanical impact of the advanced gastric simulator on hydrophilic matrix tablets and to investigate the effect of stomach transit on the tablet and how it affects the release kinetics. We also investigated the impact of the biorelevant fasted state simulated gastric fluid compared to 0,01M HCl with ions in both devices. Firstly, we were using texture analyser to measure gel thickness of two tablet formulations with different composition. We measured a reduction in gel layer thickness after swelling in the advanced gastric simulator compared to the paddle dissolution apparatus. Advanced gastric simulator passes strong mechanical and hydrodynamic forces directly onto the surface of the swelled samples, thus removing the surface layers of the matrix more effectively. The erosion of gel layer is also more pronounced compared to the paddle dissolution apparatus. The choice of the biorelevant medium does not have a significant impact on the gel thickness and erosion. Moreover, we investigated the influence of the advanced gastric simulator and intestine model for simulating peristaltic action on the release of dipyridamole from a new formulation. The in vivo pressure conditions in the lumen of the stomach and the small intestine were imitated relatively good by both devices. Consequently, dipyridamole release kinetics was faster and the total release was greater than in the paddle dissolution apparatus. Furthermore, the pH gradient was determined within the gel layer of the formulation in both devices using a complex cryostatic method. Our results showed significant differences in the release processes of tested pharmaceutical forms in classical and biorelevant apparatuses. These differences were also explained by the use of advanced analytical technologies, such as the surface pH measurements and texture analysis.

Keywords:Advanced gastric simulator, texture analyser, hydrophilic matrix system, mechanical stress, pH gradient

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