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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.

Za zdravljenje se največ uporabljajo zdravila v obliki tablet. Farmacevtska industrija stremi k poenostavitvi in s tem znižanju cen proizvodnje tablet, zaradi česar se poslužuje direktnega tabletiranja. Da je to mogoče, mora imeti tabletirna zmes ustrezne lastnosti: dobro pretočnost in stisljivost. Bistven vpliv na te lastnosti imajo uporabljene pomožne snovi, ki jih lahko predhodno obdelamo, npr. s ko-procesiranjem, in s tem izboljšamo fizikalne lastnosti, pomembne za tabletiranje. Namen magistrske naloge je bila priprava nove ko-procesirane pomožne snovi in njeno vrednotenje. Uporabili smo dve različni metodi ko-procesiranja: visokostrižno granulacijo in valjčno kompaktiranje. Pripravljenim materialom smo ovrednotili pretočne lastnosti, porazdelitev velikosti delcev, njihovo morfologijo in stisljivost ter jih primerjali z izhodno fizikalno zmesjo Harke Plus Tab Prime in dvema referenčnima ko-procesiranima pomožnima snovema (Granfiller D in Hisorad). Pretočnost smo ovrednotili z izračunom Carrovega indeksa in Hausnerjevega razmerja, stisljivost pa z izvedbo Hecklove analize. S ko-procesiranjem smo uspeli izboljšali pretočne lastnosti izhodne fizikalne zmesi, vendar smo hkrati poslabšali stisljivost. Vzorci, pripravljeni z metodo valjčnega kompaktiranja, so dosegali najboljšo pretočnost, a tudi najslabšo kompresibilnost, njihova porazdelitev velikosti delcev pa je bila zelo široka in bimodalna. Vzorci, ko-procesirani z visokostrižno granulacijo, so imeli ozko unimodalno porazdelitev velikosti delcev in dobre pretočne lastnosti. Stisljivost je bila boljša kot pri vzorcih, pripravljenih z metodo valjčnega kompaktiranja, a slabša od stisljivosti izhodne fizikalne zmesi. Najboljše fizikalne lastnosti je dosegal vzorec Harke HS#20, katerega pretočnost je boljša napram izhodni zmesi, stisljivost (kompresibilnost in kompaktibilnost) pa nekoliko slabša, a primerljiva. Ugotovili smo, da je v našem primeru visokostrižna granulacija bolj primerna metoda ko-procesiranja od valjčnega kompaktiranja. S ko-procesiranjem smo uspeli izboljšati nekatere fizikalne lastnosti, predvsem pretočne lastnosti. Vseeno pa moramo razmisliti o smiselnosti tega dodatnega procesa, saj smo ugotovili, da ima izhodna fizikalna zmes Harke Plus Tab Prime že v osnovi zelo dobre fizikalne lastnosti, primerne za direktno tabletiranje. Tablets are the most common dosage form for treatment in medicine. The aim of pharmaceutical industry is to simplify production and thus lower production prices by using direct tableting. To achieve this, the tablet mixture must have the appropriate properties: good flowability and compressibility. These properties are significantly influenced by the properties of the excipients used. Excipients can be pre-treated, e.g. by co-processing, thereby improving the physical properties important for tableting. The purpose of the master's thesis was the preparation of a new co-processed excipient and its evaluation. We used two different co-processing methods: high shear granulation and roller compaction. The prepared materials were evaluated for flow properties, particle size distribution, morphology, compressibility and compactability. Based on these properties, the prepared materials were compared with the physical mixture Harke Plus Tab Prime and two reference co-processed excipients (Granfiller D and Hisorad). Flowability was evaluated by calculating the Carr index and Hausner ratio, compressibility and compactablity by performing Heckel analysis. By co-processing, we managed to improve the flow properties of the Harke Plus Tab Prime, but at the same time we slightly worsened compaction properties (compressibility and compactability). Samples prepared by the roller compaction method achieved the best flowability but also the worst compressibility. Their particle size distribution was very broad and bimodal. Samples prepared by the high shear granulation method had a narrow unimodal particle size distribution and good flow properties. Compaction properties of materials prepared with high shear granulation were better compared to the samples prepared by roller compaction method, but worse than the Harke Plus Tab Prime. The best physical properties were achieved by the Harke HS#20 sample, whose flowability was better compared to the Harke Plus Tab Prime, and its compressibility and compatibility were slightly worse but comparable. We found that in our case high shear granulation is a more suitable method of co-processing than roller compaction. By co-processing, we were able to improve some physical properties, especially flow properties. However, we need to reconsider the benefit of this additional process, as we have found that the physical mixture Harke Plus Tab Prime already has very good physical properties, suitable for direct tableting.