Vpliv lastnosti pomožnih snovi in procesnih parametrov na kritične atribute kakovosti tablet, pripravljenih s praškovno-brizgalno tehnologijo

Zrimšek, Anja (author), Dreu, Rok (mentor), Lavrič, Zoran (comentor)

Trirazsežno tiskanje je področje novih tehnologij, ki omogoča pripravo personaliziranih enoenotnih trdnih farmacevtskih oblik z dograjevanjem po plasteh. Po odobritvi prvega 3D tiskanega zdravila Spritam s strani FDA, je tehnologija 3D tiskanja postala predmet precejšnjega zanimanja med raziskovalci. V magistrski nalogi smo se osredotočili na praškovno-brizgalno tehnologijo tiskanja tablet. Pri tej tehnologiji se trdne farmacevtske oblike gradijo z dodajanjem praškastega materiala v plasteh, ki jih poveže vezivna tekočina, ki jo s pomočjo šob tiskalnika nanašamo v obliki drobnih kapljic na vsako novo nanešeno plast prahu. Načrt za tablete izdelamo v računalniškem programu, kamor vnesemo dimenzije in obliko tablet ter procesne parametre tiskanja. S praškovno-brizgalno tehnologijo smo izdelovali tablete s pomočjo namensko razvitega 3D tiskalnika PicoJet. V prvem delu magistrske naloge smo pripravili tri procesibilne vezivne tekočine in zasnovali ustrezno zmes praškov. Vezivna tekočina je bila sestavljena iz različnih razmerij vode in etanola. Pri zasnovi vezivne tekočine smo upoštevali, da so za uspešno nanašanje vezivne tekočine pomembne: gostota, površinska napetost ter viskoznost tekočine. Končno zmes praškov za tiskanje je sestavljala modelna učinkovina ketoprofen, vodotopni polnili laktoza in manitol, vezivo polivinilpirolidon K25 in drsilo Syloid 244 FP za boljšo pretočnost. Pretočnost praškovne zmesi ima pomembno vlogo, saj delci lahko zaostajajo v zalogovniku tiskalnika in se pomanjkljivo nanesejo na delovno površino tiska. V drugem delu smo s pomočjo načrtovanja eksperimentov preučili vpliv procesnih parametrov in sestave vezivne tekočine na mehanske lastnosti izdelanih tablet. Spoznali smo, da imata višina plasti nasutja praškaste zmesi in številčna gostota aktivnih šob tiskalne glave največji vpliv na mehanske lastnosti tablet (trdnost, krušljivost in razpadnost). Nižja kot je višina plasti in višja kot je gostota aktivnih šob, bolj so pripravljene tablete kompaktne. Po drugi strani pa se je izkazalo, da vezivna tekočina nima izrazitega vpliva na mehanske lastnosti.

• Language: Slovenian
• Keywords: 3D tiskanje, personalizirana zdravila, načrtovanje eksperimentov, orodisperzibilne tablete, praškovno-brizgalna tehnologija
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-136923
• Publication date in RUL: 25.05.2022

Secondary language

• Language: English
• Title: Influence of excipient characteristics and process parameters on critical quality attributes of tablets prepared by powder bed jetting

Abstract

The three-dimensional printing is an area of new technologies that enables a development of personalized drug delivery systems, where compounds are added layer by layer. After the approval of the first 3D printed drug Spritam by the FDA, 3D printing technology became the subject of interest among researchers. In the thesis we focused on the powder bed jetting technology. This technology enables the production of solid dosage forms by adding powdered material in layers, bound together by a binder fluid, which is applied in the form of tiny droplets to each newly applied layer of powder using a printer nozzle. The design of experiments is created with a computer program, in which we define dimensions, tablet shape and printing process parameters. We produced tablets with powder bed jetting technology using the purpose-developed PicoJet 3D printer. In the first part of the thesis, we prepared three processable binder fluids and designed a suitable powder mixture. The binder fluid was composed of water and ethanol in different ratios. During the design of a liquid binder we considered that important parameters for successful application of the liquid binder are: density, surface tension and viscosity of the liquid. The final powder mixture for printing was prepared from the model drug ketoprofen, water-soluble fillers lactose and mannitol, PVP K25 binder and glidant Syloid 244 FP was added for a better flowability. The flowability of the powder mixture plays an important role, as the particles can lag in the storage tank and are consequently poorly applied to the work surface. In the second part, we evaluated the impact of process parameters and binder fluid composition on the mechanical properties of the manufactured tablets with the help of the design of experiments. We determined that the height of the filling layer of the powder mixture and the active nozzle density of the printing head have the greatest impact on the mechanical properties of the tablets (hardness, friability, disintegration). The lower the filling layer height and the higher the active nozzle density, the higher is the compactibility of the produced tablets. On the other hand, we showed that the binder fluid does not have a significant impact on the mechanical properties.

• Keywords: 3D printing, personalized medicine, design of experiments, orodispersible tablets, powder bed jetting