Optimizacija izbranih ključnih pogojev za sproščanje v umetnem želodčnem simulatorju naslednje generacije

Šentjurc, Alenka (author), Trontelj, Jurij (mentor), Vrbanac, Helena (comentor)

Z biorelevantnimi aparaturami za testiranje sproščanja želimo v čim večji meri posnemati pogoje znotraj gastrointestinalnega trakta, kar nam omogoča boljšo napoved obnašanja farmacevtske oblike (FO) in vivo. Osrednji namen magistrske naloge je bil ovrednotiti delovanje ene izmed birelevantnih aparatur, in sicer umetnega želodčnega simulatorja druge generacije (ang. »Advanced Gastric Symulator«, AGS2) razvitega s sodelovanjem podjetji Lek d.d. in Merel d.o.o. Najprej nas je zanimalo v kolikšni meri se, predvsem glede zmožnosti ustvarjanja mehanskega stresa na vsebino, novi model razlikuje od starega (AGS1) in kakšne so te vrednosti v primerjavi z dostopnimi podatki iz literature, pridobljenimi in vivo. Tlak smo merili s telemetrično kapsulo SmartPill® pri več različnih nastavitvah delovanja naprav in v dveh različnih silikonskih vrečah. Rezultati presenetljivo kažejo, da je AGS1 nekoliko močnejši tako v kombinaciji z ozko kot tudi s široko vrečo. Variabilnost rezultatov je pri obeh napravah manjša ob uporabi ozke vreče, ne moremo pa trditi, da kateri od modelov splošno zagotavlja konstantnejše meritve tlakov. V primerjavi s povprečnimi vrednostmi in vivo v želodcu na tešče so tlaki pri obeh AGS nekoliko nižji, vendar še vedno v istem velikostnem razredu, medtem ko vrednosti po obroku ne moremo doseči z nobeno od aparatur. Večjo moč AGS1 smo v nadaljevanju pokazali še na praktičnem primeru razgradnje testenin, ki jih je ta, še posebej v kombinaciji s široko vrečo, zdrobil na precej manjše delce. Zanimivo pa v kombinaciji z ozko vrečo razlika niti ni bila tako izrazita, čeprav je bil s SmartPill® izmerjeni tlak v AGS2 v primeru izvajanja enakega programa z ozko vrečo, skoraj 100 mmHg manjši kakor v AGS1. V zaključnem delu smo opazovali še podaljšano sproščanje učinkovine iz dveh testnih formulacij različne sestave (hidrofilne ogrodne tablete s polietilenoksidom). Pri tem smo za obe formulaciji uporabili USP2 napravo s hitrostjo vrtenja mešala 50 in 75 rpm, nato pa za prvo še štiri različne programe gibanja zaslonk AGS2, na vsaki izmed dveh vreč. Drugo smo s pomočjo novega umetnega želodca testirali le na skrajnih primerih, ki sta pri prvi formulaciji povzročila najhitrejše in najpočasnejše sproščanje. Ugotovili smo, da za razliko od USP2 s spremembo različnih parametrov AGS2 dobimo tudi širok nabor različnih profilov sproščanja, pri katerih je po 5 urah delež sproščene učinkovine nekje med 52,9 % in 102,4 %. V nadaljevanju smo na enem od skrajnih primerov tudi pravilno pokazali nekoliko hitrejši profil sproščanja za drugo formulacijo.

• Language: Slovenian
• Keywords: umetni želodčni simulator, SmartPill®, tlak, poskusi sproščanja, tablete s podaljšanim sproščanjem
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-136926
• Publication date in RUL: 25.05.2022

Secondary language

• Language: English
• Title: Optimisation of critical dissolution parameters of a next generation advanced gastric simulator

Abstract

Using biorelevant apparatuses for dissolution testing, we try to closely mimic the conditions inside the gastrointestinal tract, which allows us to better predict the in vivo behaviour of the dosage form. The main purpose of the Master's thesis was to evaluate the working ability of one biorelevant apparatus ⠒ the artificial gastric simulator of a second generation (Advanced Gastric Simulator, AGS2), developed in cooperation of Lek d.d. and Merel d.o.o. Firsty, we were interested to what extent, especially in terms of the ability to produce mechanical stress on its content, the new model differs from the old one (AGS1) and if these values are comparable to available in vivo literature data. We measured the pressure with a telemetric capsule Smartpill® at several different operating settings of the both devices and in two different silicone bags. Surprisingly, the results show that AGS1 is somewhat stronger in combination with both a narrow and a wide bag. Variability of the results is lower on both apparatuses when using a narrow bag, but we cannot claim that either of the models generally provides more constant pressure measurements. Compared to the average in vivo values of the fasted stomach, the pressures in both models are slightly lower, however, still in the same magnitude range. Postprandial values on the other hand, can not be achieved with either one of the apparatuses. We further demonstrated a greater strength of the AGS1 on a practical example of the decomposition of pasta, which was, especially in combination with a wide bag, broken down into much smaller particles using that model. Interestingly, the difference was not as significant in combination with a narrow bag, although the pressure measured by the SmartPill® in the AGS2 while implementing the same program with a narrow bag was almost 100 mmHg lower than in the AGS1. For the final part, we observed a prolonged release of the active ingredient from two test formulations (polyethylene oxide matrix tablets) with a different composition. We used a USP2 with a stirring speed of 50 and 75 rpm in the case of both tested formulations, and then for the first one another four different aperture movement programs on each of the AGS2 bags. The second one was only tested at extreme conditions in the new gastric simualtor, which caused the fastest and the slowest release from the first formulation. As observed, with a variation of different AGS2 parameters, a wide range of different dissolution profiles were obtained, which was not the case in the USP2 apparatus. The proportion of the released active ingredient in AGS2 after 5 hours was somewhere between 52,9 % and 102,4 %. We also correctly demonstrated a slightly faster dissolution profile for the second formulation with one of the extreme testing settings.

• Keywords: advanced gastric simulator, SmartPill®, pressure, dissolution testing, prolonged release tablets