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Pri proizvodnji tablet si želimo z robustnim proizvodnim procesom izdelati kakovosten izdelek z ustreznimi mehanskimi lastnostmi. Slabša stisljivost zmesi za tabletiranje je pogosto problematična tekom tabletiranja, zato je treba že med razvojem izdelka ovrednoti spremenljivke, ki imajo nanjo največji vpliv. V eksperimentalnem delu magistrske naloge smo s pomočjo instrumenta za analizo stisljivosti zmesi Gamlen preučevali, kako se tabletabilnost, kompaktibilnost in kompresibilnost granulata, izdelanega s kompaktiranjem, spremenijo pod vplivom sestave in načina priprave vzorcev. Analizirali smo realne zmesi za tabletiranje, ki so bile pripravljene z enim najpogostejših postopkov suhega granuliranja – kompaktiranjem. Zanimalo nas je, ali prametri kompaktiranja, uporabljen tip mlina (oscilacijski mlin, mlin kladivar, konični mlin) in izbrani parametri mletja vplivajo na partikulatne in mehanske lastnosti nastalih granul. Poleg tega smo preučili tudi vpliv dveh pogosto uporabljenih polnil, mikrokristalne celuloze in laktoze, ki se bistveno razlikujeta v prevladujočem mehanizmu deformacije (plastična deformacija ali deformacija s fragmentiranjem delcev). Izkazalo se je, da ima izbor polnila največji vpliv tako na fizikalne kot tudi mehanske lastnosti vzorcev, saj se je mikrokristalna celuloza pričakovano pokazala kot bolj tabletabilna, kompaktibilna in kompresibilna. Dokazali smo tudi negativen vpliv daljše izpostavljenosti silam pri kompaktiranju na stisljivost in mehanske lastnosti granul. Izbira tipa mlina in parametri mletja so vplivali predvsem na velikost delcev granulata, slednja se je nakazovala kot lastnost, ki ima učinek na tabletabilnost, kompaktibilnost in kompresibilnost zmesi za tabletiranje. Neposrednega vpliva pogojev mletja na stisljivost nam ni uspelo potrditi, saj so se ti največkrat izrazili le preko velikosti delcev. In tablet manufacturing, a product with adequate mechanical properties is required to achieve desired quality and robustness of the tableting phase. Poorer compaction properties can be problematic during tableting, so it is necessary to evaluate variables that have the greatest impact during product development. As part of the master's thesis, we studied how tabletability, compactibility and compressibility change under the influence of the composition and granulate preparation, using Gamlen instrument – a system for powder compaction analysis. We analyzed real compression mixtures, prepared by one of the most common dry granulation processes - roller compaction. We were interested in whether the compaction parameters, different types of mills (oscillating mill, hammer mill, conical mill) and different milling parameters affect the particulate and mechanical properties of the granules. In addition, we also compared the influence of two commonly used pharmaceutical fillers, i.e. plastically deforming microcrystalline cellulose and fragmenting lactose. It was found that the type of filler used has the greatest impact on both physical and mechanical properties of granules, where microcrystalline cellulose proved to contribute to better tabletability, compactibility and compressibility of produced granules. We also demonstrated the negative impact of prolonged exposure to mechanical forces during roller compaction on the compaction and also mechanical properties of the samples. The type of mill and milling parameters used in our work mainly influenced granule size, and the latter appeared to be a property that highly affected tabletability, compactability and compressibility of the compression mixtures. However, we were unable to directly confirm influence of milling conditions on the compaction properties, as they were mostly expressed only through the particles size. |
