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Študij vpliva procesnih parametrov kontinuiranega vlažnega granuliranja v dvopolžni napravi na lastnosti zrnc in primerjava s šaržnimi procesi granuliranja
ID Rotar Pucko, Eva (Avtor), ID Dreu, Rok (Mentor) Več o mentorju... Povezava se odpre v novem oknu, ID Lavrič, Zoran (Komentor)

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Izvleček
Temeljna zahteva farmacevtske industrije je izdelava kakovostnih, varnih in učinkovitih zdravil. Na tem področju prevladujejo klasični šaržni proizvodni procesi, v zadnjem času pa se zaradi naraščajočih potreb po večji časovni in cenovni učinkovitosti ter prilagodljivosti potrebam trga uveljavlja tudi kontinuirana proizvodnja zdravil. Ta je podprta z regulatornimi smernicami in izsledki izčrpnih raziskav v preteklem desetletju, njen nadaljnji intenzivni razvoj pa se obeta tudi v prihodnje. V magistrski nalogi smo podrobno proučili proces kontinuiranega vlažnega granuliranja, saj je korak granulacije nemalokrat kritičen in nujno potreben v proizvodnji trdnih farmacevtskih oblik. Posvetili smo se primerjavi zrnc enake sestave, izdelanih v kontinuiranem procesu na dvopolžnem granulatorju ter v šaržnih procesih na vrtinčnoslojnem in hitro vrtečem granulatorju. Z variiranjem ključnih procesnih parametrov smo ovrednotili njihov vpliv na kritične lastnosti zrnc, ki vplivajo na nadaljnji proces tabletiranja in kakovost nastalih tablet. Potrdili smo, da izbrana tehnologija pomembno vpliva na lastnosti nastalih zrnc. Z dvopolžno napravo smo izdelali zrnca različnih oblik: od povsem nepravilnih do podolgovatih s prisekanimi ravnimi površinami in bolj ali manj sferičnih. Njihova porazdelitev velikosti je bila široka in bimodalna, zlasti pri skrajnih vrednostih masnega pretoka zmesi prahov in hitrostih vrtenja polžev, ki so bili izven optimalnega območja procesnih parametrov. Tovrstna zrnca so bila zmerno pretočna in stisljiva, tablete, ki smo jih iz njih izdelali, pa so ustrezale farmakopejskemu preskusu krušljivosti neobloženih tablet. V vrtinčnoslojnem granulatorju smo izdelali med seboj zelo primerljive vzorce zrnc z ozko porazdelitvijo velikosti, nizko nasipno gostoto, slabšo pretočnostjo in zelo dobro stisljivostjo. Zaradi predhodnega raztapljanja in posledično bolj enakomerne razporeditve veziva v strukturi zrnc so bila ta v primerjavi z ostalimi vzorci občutno bolj kompaktibilna, nastale tablete pa najmanj krušljive. Zrnca, izdelana v hitro vrtečem granulatorju, so bila bolj sferična in kompaktna ter imela bolj gladko površino. Pri procesu tabletiranja so bila najmanj stisljiva, nastale tablete pa niso ustrezale farmakopejskemu preskusu krušljivosti neobloženih tablet, saj so bila tabletna jedra ob koncu preskusa vidno okrušena, v nekaterih primerih pa je bil razviden tudi lom tablete. Na podlagi rezultatov vsebnosti barvila tartrazin v stisnjenih tabletah nismo mogli oblikovati pomembnejših zaključkov, saj so bili ti ustrezni in primerljivi za vse izdelane vzorce. Pokazali smo, da ob nadaljnji optimizaciji kontinuirano dvopolžno granuliranje predstavlja potencialno alternativo klasičnima šaržnima procesoma, lastnosti tako izdelanih zrnc pa so kompromis med stisljivostjo in pretočnostjo, kot ju zagotavljata klasični šaržni tehnologiji granuliranja.

Jezik:Slovenski jezik
Ključne besede:kontinuirana proizvodnja, vlažno granuliranje, dvopolžni granulator, vrtinčnoslojni granulator, hitro vrteči granulator, pretočnost, kompaktibilnost, kompresibilnost
Vrsta gradiva:Magistrsko delo/naloga
Organizacija:FFA - Fakulteta za farmacijo
Leto izida:2023
PID:20.500.12556/RUL-149749 Povezava se odpre v novem oknu
Datum objave v RUL:09.09.2023
Število ogledov:724
Število prenosov:39
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Sekundarni jezik

Jezik:Angleški jezik
Naslov:A study of the impact of process parameters of continuous twin-screw wet granulation on granule properties and comparison with batch granulation processes
Izvleček:
The fundamental requirement of the pharmaceutical industry is the production of high-quality, safe, and effective medications. Traditionally, batch manufacturing has been the predominant method in this field. However, due to the increasing need for improved time and cost efficiency, as well as fast adaptability to market demands, continuous manufacturing has recently gained importance. It is supported by regulatory guidelines and extensive research from the last decade, and further development is expected. In this master's thesis, we focused on continuous wet granulation because the granulation process is often a necessary and critical step in the production of solid pharmaceutical dosage forms. We compared granules of the same composition produced in a continuous twin-screw granulator with those produced in a batch fluidized bed and high shear granulator. By varying key process parameters, we evaluated their impact on critical granule properties, which in turn directly affected the subsequent tableting process and the overall quality of the resulting tablets. We confirmed that the selected method of granulation affected the properties of the produced granules. Using the twin-screw granulator, we produced granules of various shapes, from elongated and flat to spherical and completely irregular. The size distribution was wide and bimodal, especially at extreme values of the powder flow rate and screw speed, which were outside the optimal range. The granules exhibited moderate flowability and compressibility, with low friability of the tablets produced. In contrast, using a fluidized bed granulator, we were able to produce granules that had a similar size distribution, low bulk density, poor flowability, and high compressibility. Due to the dissolution and the resulting uniform distribution of the binder in the granule structure, they exhibited significantly improved compactibility compared to the other samples, and resulted in tablets that exhibited minimal friability. In contrast, granules from high shear granulation were densely compacted, possessed a spherical morphology, and exhibited a smooth surface. They displayed the lowest compressibility. In addition, the resulting tablet cores did not meet the requirements of the pharmacopoeial friability test for uncoated tablets, as they were visibly chipped at the end of the test, and in some cases, fractures were also evident. We were not able to draw any significant conclusions from the results of tartrazine content in compressed tablets, as they were satisfactory and comparable for all samples produced. In conclusion, we have shown that, with further optimization, continuous twin-screw granulation is a potential alternative to conventional batch processes, with the properties of the granules produced representing a reasonable compromise between compressibility and flowability.

Ključne besede:continuous manufacturing, wet granulation, twin-screw granulator, fluidized bed granulator, high shear granulator, flowability, compactibility, compressibility

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