Vpliv procesnih parametrov valjčnega kompaktiranja in sestave zmesi na lastnosti izdelanih zrnc in tablet

Čučnik, Brina (author), German Ilić, Ilija (mentor), Jeraj, Žiga (comentor)

Veliko farmacevtskih zmesi nima ustreznih lastnosti za direktno tabletiranje, zato je pogosto potrebna predhodna obdelava delcev z granuliranjem. Ena od možnosti je suho granuliranje z valjčnim kompaktiranjem, ki z uporabo zunanjega tlaka poveča velikost delcev in izboljša pretočnost. Cilj naloge je bil ovrednotiti vpliv procesnih parametrov valjčnega kompaktiranja in sestave zmesi na lastnosti izdelanih zrnc in tablet. Izvedli smo več poskusov valjčnega kompaktiranja na dveh zmeseh z različnim razmerjem med mikrokristalno celulozo in brezvodno laktozo, s čimer smo primerjali vpliv dveh različnih deformacijskih mehanizmov materiala. V zmesi MCC prevladuje mikrokristalna celuloza, ki je izrazito plastična, v zmesi LAK pa brezvodna laktoza, ki je bolj lomljiva. Raziskali smo tudi, kako sila valjčnega kompaktiranja, razmik med valjema, hitrost vrtenja in vrsta valjev vplivajo na lastnosti kompaktnih trakov, porazdelitev velikosti izdelanih zrnc, njihove pretočne lastnosti ter tabletabilnost, krušljivost in razpadnost tablet. Sestava zmesi je bistveno vplivala na navidezno gostoto kompaktnih trakov, nasipno in zbito gostoto zmesi in zrnc ter pretočne lastnosti. Zrnca LAK so dosegala višje vrednosti gostot, masni pretok pa je bil večji pri vzorcih MCC. Vrsta zmesi je imela ključni vpliv tudi na tabletabilnost, ki je bila večja pri plastično deformirajočih zrncih MCC. Večja sila valjčnega kompaktiranja je negativno vplivala na tabletabilnost, vendar pa je omogočila nastanek večjih zrnc z boljšimi pretočnimi lastnostmi. Tablete MCC so razpadale hitreje kot tablete LAK, sila valjčnega kompaktiranja pa je imela pri obeh zmeseh nasproten vpliv na čas razpadnosti. Krušljivost tablet je bila med vzorci primerljiva in odvisna predvsem od sile tabletiranja. Manj vplivni procesni parametri so bili razmik med valjema, ki je vplival predvsem na delež prašne frakcije, ter hitrost in vrsta valjev, ki se pri obdelavi zmesi s pretežno fragmentirajočim mehanizmom deformacije nista izkazali kot pomembna. Ključna dejavnika, ki sta vplivala na proučevane lastnosti, sta bila sestava zmesi in sila valjčnega kompaktiranja. Pri načrtovanju valjčnega kompaktiranja je pomembno doseči ravnovesje med izboljšanjem pretočnosti zrnc in ohranjanjem njihove tabletabilnosti. Ustrezne procesne pogoje je zato treba izbrati glede na lastnosti zmesi in njen deformacijski mehanizem.

• Language: Slovenian
• Keywords: suho granuliranje, valjčno kompaktiranje, mikrokristalna celuloza, brezvodna laktoza, sila valjčnega kompaktiranja, tabletabilnost
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2026
• PID: 20.500.12556/RUL-187641
• Publication date in RUL: 12.09.2026

Secondary language

• Language: English
• Title: Influence of roller compaction process parameters and blend composition on the properties of the produced granules and tablets

Abstract

Many pharmaceutical powders lack the properties required for direct compression and need to undergo granulation prior to tableting. One option is dry granulation by roller compaction, which increases particle size and improves flowability through the application of external pressure. The aim of this thesis was to evaluate the effects of roller compaction process parameters and blend composition on the properties of the resulting granules and tablets. We performed several roller compaction experiments using two blends with different ratios of microcrystalline cellulose and anhydrous lactose to compare two different deformation mechanisms. The MCC blend contained predominantly microcrystalline cellulose, which mainly undergoes plastic deformation, whereas the LAK blend contained predominantly anhydrous lactose, which is more prone to fragmentation. The effects of roller compaction force, roll gap, roll speed, and roll surface type on ribbon properties, granule particle size distribution, and flow properties were investigated. Tabletability, friability, and disintegration of the tablets were also evaluated. Blend composition had a great effect on ribbon relative density, the bulk and tapped densities of the blends and granules, and flow properties. LAK granules had higher bulk and tapped densities, whereas MCC granules showed a higher mass flow rate. Blend composition also had a major effect on tabletability, which was greater for the plastically deforming MCC granules. Increasing the roller compaction force reduced tabletability but produced larger granules with better flowability. MCC tablets disintegrated faster than LAK tablets, while roller compaction force had opposite effect on their disintegration time. Tablet friability was comparable among the samples and was primarily influenced by tableting force. Less influential process parameters were the roll gap, which mainly affected the amount of fines, while roll speed and roll surface type had no significant effect when processing a predominantly fragmenting blend. The key factors affecting the investigated properties were blend composition and compaction force. In roller compaction, it is important to achieve a balance between improving granule flowability and maintaining their tabletability. The process conditions should consequently be selected according to the properties of the blend and its deformation mechanism.

• Keywords: dry granulation, roller compaction, microcrystalline cellulose, anhydrous lactose, roller compaction force, tabletability