Vrednotenje korelacij med izbranimi cenilkami pretočnih lastnosti tabletne zmesi praškov in stabilnostjo procesa tabletiranja z vidika mase tablete

Nahtigal, Nastja (author), Dreu, Rok (mentor), Bukovec, Polona (co-mentor)

Pretočne lastnosti prahov imajo ključen pomen med tehnološkimi postopki, predvsem pri procesu tabletiranja, pri katerem je od pretočnih lastnostih tabletne zmesi odvisno ustrezno polnjenje matrične vdolbine in posledično enakomernost mase tablet. Pretočne lastnosti smo vrednotili vzorcem polnil, t.j. različnim vrstam manitolov, mikrokristalnih celuloz in laktoz ter še njihovim realnim tabletnim zmesem, in sicer s Carrovim indeksom, Hausnerjevim razmerjem, Beverloo parametrom ter s cenilkami metode vrtečega bobna, praškovnega reometra in enote za karakterizacijo delcev Hosokawa PT-X. Z metodami vrednotenja pretočnih lastnosti praškastih vzorcev smo potrdili, da je pretočnost boljša, kadar so delci prahu večji in bolj sferičnih oblik. Ugotovili smo, da ni mogoča le enoznačna opredelitev pretočnih lastnosti praškastih vzorcev, kar potrjuje, da je pretočnost prahov odvisna od številnih fizikalnih dejavnikov, ki med seboj interagirajo kompleksno. Z oblikovanjem realnih zmesi za direktno tabletiranje smo izboljšali pretočne lastnosti predvsem slabše pretočnih polnil. Negativen vpliv dodanih komponent na pretočnost zmesi smo ugotovili predvsem pri zmeseh na osnovi dobro pretočnih polnil. Najbolj signifikantne spremembe pretočnosti med polnili in njihovimi zmesmi smo pokazali z metodama praškovnega reometra in vrtečega bobna, z metodama Carrovega indeksa in Hausnerjevega razmerja pa najmanj. Ugotovili smo, da samo na osnovi polnil ne moremo napovedati obnašanja končne zmesi za tabletiranje, čeprav gre za prevladujočo komponento zmesi. Iz pripravljenih zmesi smo s postopkom direktnega tabletiranja na rotacijski tabletirki stisnili tablete in vrednotili stabilnost procesa tabletiranja z vidika variiranja mase. Potrdili smo, da je slabša stabilnost procesa tabletiranja povezana s slabšo pretočnostjo tabletne zmesi. Stabilnost postopka direktnega tabletiranja smo najbolje napovedali z metodo vrtečega bobna in praškovnega reometra, predvsem s cenilkama kot po plazenju in kohezijski indeks. Za proces tabletiranja merodajne rezultate smo dobili tudi z analizatorjem pretočnih lastnosti Hosokawa PT-X, predvsem z metodo nasipnega kota. Beverloo parameter smo opredelili kot najmanj primerno cenilko, predvsem zaradi neprimernosti analize prahov s slabšo pretočnostjo.

• Language: Slovenian
• Keywords: pretočne lastnosti, metoda vrtečega bobna, Beverloo parameter, praškovni reometer, nasipni kot, mikrokristalna celuloza, manitol, laktoza, direktno tabletiranje
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-121255
• Publication date in RUL: 02.10.2020

Secondary language

• Language: English
• Title: Assessment of correlations between selected parameters of powder tableting mixture flow properties and stability of the tableting process according to the tablet mass

Abstract

Flow properties of powders have an important impact during technology processes, especially in case of tableting, where the proper die-filling and constant tablet weight require adequate flow properties of the tableting mixture. Flow properties of different types of fillers, i.e. of mannitol, microcrystalline cellulose and lactose and their realistic mixtures were determined with Carr index, Hausner ratio, Beverloo parameter and with different rotating drum, powder rheometer and Hosokawa Powder Tester PT-X powder flow estimators. With methods used to assess flow properties of powder samples, we confirmed that the ability to flow is better when powder particles are larger and more spherical. It was found that it is not possible to define the flow properties of powder samples in absolute manner, which confirms that the powder flow depends on a number of factors that interact in a complex way. By preparing realistic mixtures for direct compression, we improved the overall flow properties, especially in case of fillers with poorer powder flow. The negative effect of added components on the powder tableting mixture flow properties was found mainly in mixtures based on well-flowing fillers. The most significant changes in results of fillers and their mixtures were demonstrated by the powder rheometer and rotating drum method, and the least by Carr index and Hausner ratio. It was found that one cannot reliably predict the behavior of the tableting mixture only on the basis of predominant component – e.g. fillers. Tablets of different tableting mixtures were pressed in the direct tableting process using a rotary tablet press. The stability of the tableting process was evaluated by assessing the tablet mass variability. We confirmed that the poorer process stability is associated with poorer flow properties of the tableting mixture. The direct tableting process stability was most adequately predicted by the rotating drum method and by powder rheometer, mainly by the rest angle and the cohesion index. Results that were significant for tableting were obtained also with the Hosokawa Powder tester PT-X, mainly by the angle of repose. The Beverloo parameter was defined as the least suitable parameter, mainly due to the inadequacy of the analysis of powders with poorer flow properties.

• Keywords: flow properties, rotating drum method, Beverloo parameter, powder rheometer, angle of repose, microcrystalline cellulose, mannitol, lactose, direct tableting process