Proučevanje vpliva procesnih parametrov radialnega iztiskanja in filmskega oblaganja na izbrane lastnosti obloženih iztiskancev

Gradišek, Aljoša (author), Vrečer, Franc (mentor), Korasa, Klemen (comentor)

Iztiskanje s krogličenjem je ena najpogosteje uporabljanih metod izdelave pelet v farmacevtski industriji, ki omogoča izdelavo kompaktnih pelet z ozko porazdelitvijo velikosti delcev in nizko krušljivostjo, kar so njihove pomembne lastnosti pri filmskem oblaganju. Gre za kompleksen proces v katerem nastopa veliko število procesnih parametrov, zato je, z namenom povečanja učinkovitosti, smiselno uporabiti načrtovanje eksperimentov (DoE), s katerim lahko preverimo vpliv večjega števila parametrov hkrati ter na podlagi izbranih procesnih parametrov napovemo lastnosti končnega izdelka. Pelete najpogosteje filmsko oblagamo v vrtinčnoslojnem oblagalniku z razprševanjem od spodaj. Določanje končne točke oblaganja glede na porabo disperzije za oblaganje lahko vodi do visoke variabilnosti debeline obloge med serijami, zato se vedno bolj uveljavlja spremljanje procesov v realnem času, ki omogoča večjo ponovljivost doseganja ustrezne, ciljne debeline filmske obloge. S pomočjo metode načrtovanja eksperimentov smo določili optimalne procesne parametre radialne ekstruzije, količino vode v zmesi za iztiskanje, velikost odprtin matrice za iztiskanje in hitrost noža za iztiskanje, za izdelavo iztiskancev primernih za filmsko oblaganje. Cilj je bil izdelati kar se da okrogle iztiskance, z ozko porazdelitvijo delcev in nizko krušljivostjo. Kot optimalne procesne parametre smo glede na model DoE izbrali večjo matrico z odprtinami 0,8 mm, najvišjo količino vode v zmesi za iztiskanje, 110 % mase suhe snovi in najnižjo hitrost noža za iztiskanje, 15 obratov na minuto. Del iztiskancev smo pri izbranih procesnih parametrih izdelali s krogličenjem, drugi del pa smo zmleli z mlinom kladivarjem. Med filmskim oblaganjem smo vzorce odvzete pri znani porabi suspenzije za oblaganje ovrednotili z bližnje infrardeče svetlobno (NIR) sondo. Za potrditev rezultatov meritev smo v suspenzijo dodali barvilo tartrazin, katerega vsebnost v obloženih »peletah« smo določili s pomočjo ultravijolične in vidne (UV/VIS) spektroskopije. Na podlagi podatkov smo izdelali modele za napoved količine obloge, z meritvami NIR spektrov obloženih iztiskancev, ob proizvodni liniji. S simulacijo procesa oblaganja v praksi smo preverili uporabnost modela za določanje končne točke procesa. Pri oblaganju krogličenih iztiskancev smo v končni točki določeni glede na NIR meritve presegli ciljni nanos (110 %). Pri mletih iztiskancih pa smo uspeli zelo natančno zadeti ciljni nanos (100,3 %).

• Language: Slovenian
• Keywords: Iztiskanje s krogličenjem, pelete, filmsko oblaganje, procesno analizna tehnologija, načrtovanje eksperimentov, multivariatna analiza podatkov, bližnja infrardeča spektroskopija
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-128124
• Publication date in RUL: 03.07.2021

GRADIŠEK, Aljoša, 2021, Proučevanje vpliva procesnih parametrov radialnega iztiskanja in filmskega oblaganja na izbrane lastnosti obloženih iztiskancev [online]. Master’s thesis. [Accessed 25 March 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=128124

Secondary language

• Language: English
• Title: Study of radial extrusion and film coating process parameters influencing selected properties of coated extrudates

Abstract

Extrusion and spheronization is a widely used method of producing pellets. It gives us compact pellets with narrow particle size distribution and low friability, which are their important characteristics for film coating. Due to the complexity of the process, we can use advanced optimization methods such as the design of experiments, which allows us to quantify the effect of multiple process parameters and predict the characteristics of end product at chosen parameters. Pellets are usually coated in a fluid bed using the bottom spray technique. Relying on the consumption of coating dispersion to determine the process end point could cause high variability of film coating thickness. To achieve higher repeatability, real time process monitoring techniques are being increasingly applied. Using the design of experiments we have determined optimal values of following process parameters of radial extrusion: water content in granulated mass, size of extrusion screen and the extrusion speed. The goal was to produce spherical extrudates with narrow particle size distribution and low friability. Optimal process parameters according to DoE model were larger extrusion screen (0,8 x 0,7 mm), the highest water content in granulated mass (110% of dry matter mass) and the lowest extrusion speed (15 rpm). Using chosen process parameters we made a larger quantity of extrudates, part of which was later spheronized and the other part was milled using HammerWitt hammer mill. During film coating, we have measured the near infrared (NIR) spectra of coated pellet samples taken at known applied coating suspension. To further validate the results we added dye tartrazine to coating suspension and later determined its content using ultraviolet and visible (UV/VIS) spectroscopy from which we calculated the quantity of applied coating suspension. Using gathered data we've created partial least squares regression (PLS) models for the prediction of applied coating quantity by at-line NIR measurements of coated pellets. Models were tested in additional coating experiments with the goal to determine the end point using only spectral data. The end result of film coating was compared to earlier experiments in respect to the quantity of applied coating suspension and coating thickness measured by scanning electron microscope (SEM). The predicted quantity of applied coating suspension for spheronized pellets was higher (110 %) than the target value. In the case of milled pellets, we've managed to accurately predict coating quantity (100,3 %) and stop the coating process close to the target value.

• Keywords: Extrusion and spheronization, pellets, film coating, process analytical technology, design of experiments, multivariate data analysis, near-infrared spectroscopy