Primerjava robustnosti postopka filmskega oblaganja pelet brez in z medprocesnim vrednotenjem debeline obloge

Svetič, Sandi (avtor), Dreu, Rok (mentor), Brezovar, Teja (komentor)

Namen naloge je primerjava robustnosti postopka oblaganja pelet z in brez medprocesnega vrednotenja debeline obloge. Pelete smo pri različnih procesnih pogojih obložili s filmsko oblogo za dosego podaljšanega sproščanja. Eksperimente oblaganj smo izvajali v dveh delih. V prvem delu smo preverjali robustnost procesov filmskega oblaganja ob nenamernih variacijah procesnih pogojev, na katere ne moremo vplivati. Pri tem smo prvi sklop procesov vodili z medprocesnim analizatorjem PATVIS APA do referenčne debeline, drugi sklop pa smo vodili na klasičen način, do enake porabe suspenzije. Kinetiko sproščanja učinkovine smo določili s preskusom sproščanja. Profile sproščanj smo med seboj primerjali in tako preverili primerljivost posameznih serij pelet. Podobnost profilov smo numerično ovrednotili z uporabo faktorjev različnosti in podobnosti, ki smo jih izračunali za vse možne pare obloženih vzorcev pelet. V prvem delu naloge smo pokazali, da sta ob enakih izhodiščih oba načina vodenja procesa primerljivo robustna. V nadaljevanju smo želeli razložiti, zakaj se profili sproščanja pelet, ki smo jih obložili v prvem sklopu, razdelijo v dve skupini. Ugotovili smo, da skupini sovpadata z različnimi velikostmi vhodnih jeder z učinkovino. Izračunali smo teoretičen nanos filmske obloge, pri katerem bi bila hitrost sproščanja učinkovine iz različno velikih pelet enaka, in ob upoštevanju vseh relevantnih lastnosti pelet ugotovili, da imajo izbrane skupine obloženih pelet različnih velikosti že ustrezno debelino obloge. Na podlagi koreliranja procesnih spremenljivk in lastnosti pelet z deležem sproščene učinkovine po 6 urah smo ugotovili, da je za zaznane spremembe profilov vzrok sprememba vlage pelet med procesom oblaganja. V drugem delu naloge smo preverjali robustnost procesov filmskega oblaganja pri namernih variacijah procesnih pogojev. Z namernimi spremembami pogojev smo želeli vplivati na izkoristek procesa. Z dvigom vlažnosti vhodnega zraka smo povečali izkoristek procesa. Profila sproščanja pelet, obloženih brez in z medprocesnim vrednotenjem debeline sta bila medsebojno primerljiva, vendar ne tudi s profili predhodno obloženih pelet. V nadaljevanju smo zmanjšali velikost reže med distribucijsko ploščo in razmejitvenim valjem ter ločeno še za oblaganje uporabili manjšo maso vhodnih jeder ob sočasnem zmanjšanju reže med distribucijsko ploščo in razmejitvenim valjem. S temi spremembami procesnih spremenljivk smo želeli doseči zmanjšanje izkoristka oblaganja, kar pa je bilo le delno uspešno. Profili sproščanja pelet z in brez medprocesnega vrednotenja so bili tudi v tej skupini med seboj primerljivi. Na podlagi vseh zbranih rezultatov smo zaključili, da sta procesa filmskega oblaganja brez in z medprocesno kontrolo primerljivo robustna.

• Jezik: Slovenski jezik
• Ključne besede: robustnost, pelete, filmsko oblaganje, medprocesno vrednotenje debeline obloge, patvis apa, računalniški vid
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2019
• PID: 20.500.12556/RUL-111802
• Datum objave v RUL: 14.10.2019

SVETIČ, Sandi, 2019, Primerjava robustnosti postopka filmskega oblaganja pelet brez in z medprocesnim vrednotenjem debeline obloge [na spletu]. Magistrsko delo. [Dostopano 5 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=111802

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Comparison of pellet film coating robustness with and without the in-process coating thickness evaluation

Izvleček

The purpose of the thesis was to compare the robustness of the pellet coating process with and without in-process coating thickness evaluation. Pellets were coated with film coating under various conditions to achieve prolonged release. The experiments were conducted in two parts. In the first part we evaluated robustness of film coating processes, executed under the same process conditions. We controlled the first set of coating processes with the PATVIS APA in-process analyser by stopping the process when target thickness of the film coating was achieved. In the second set of experiments coating was finished, when the target mass of the suspension was sprayed onto pellets. We used the dissolution test to determine the release kinetics of active substance from pellets and analysed resulting dissolution profiles with the goal of verifying comparability of individual batches of pellets. To numerically evaluate similarity of the dissolution profiles, we calculated difference and similarity factors for all possible batch pairs. In the first part of the thesis, we showed that both methods of the process control are relatively robust. Following the results of first part, we wanted to understand why drug release profiles were divided into two distinct groups. We found that the groups coincide with different sizes of the neutral pellet cores we used for coating. We calculated the mass of coating suspension necessary to achieve the same rate of release from differently sized particles. We found out that we already sprayed appropriate amount of coating suspension to selected groups. Based on the correlation of process variables and properties of pellets with the fraction of released substance after 6 hours, we determined that observed profile changes happened due to a change in the moisture content of the pellets during the coating process. In the second part of the thesis, we tested the robustness of film coating processes under deliberate variations of process conditions. By intentionally changing the conditions, we wanted to influence the efficiency of the process. By raising the humidity of the inlet air, we have increased the yield of the process. The release profiles of pellets coated with and without an in-process thickness evaluation were comparable with each other, but not with the profiles of previous samples. We then reduced the gap between the distribution plate and Wurster partition. Separately, we coated a smaller mass of neutral pellet cores, while reducing the gap between the distribution plate and the Wurster partition. The planned reduction in the coating yield was only partially achieved. The pellet release profiles with and without in-process coating thickness evaluation were also comparable in this group. Based on all the collected results, we concluded that film coating processes with and without in-process control exhibit comparable robustness.

• Ključne besede: robustness, pellets, film coating, in-process coating thickness evaluation, patvis apa, computer vision