Priprava filamenata za izradu farmaceutskih dozirnih oblika 3D-tiskanjem

master's thesis

• Title (english): Preparation of filaments for 3D printing of pharmaceutical dosage forms
• Author: Ema Vukelić
• Mentor: Gordana Matijašić (mentor)
• Committee member: Gordana Matijašić (predsjednik povjerenstva)
• Committee member: Krunoslav Žižek (član povjerenstva)
• Committee member: Emi Govorčin Bajsić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering; Mechanical, Thermal and Separation Processes

Abstract

Razvoj medicinskih saznanja i farmaceutskog tržišta doveo je do prepoznavanja potrebe za okretanjem proizvodnje k pacijentu. 3D-pisač omogućio je proizvodnju novih personaliziranih dozirnih oblika. Razvoj takvih dozirnih oblika pretpostavlja u prvom koraku razvoj filamenata koji sadrže djelatnu tvar. Stoga je cilj ovog rada priprema filamenata koji će sadržavati dronedaron-hidroklorid (DNR), djelatnu tvar za liječenje srčane aritmije te omogućiti tiskanje tableta. U pripremi filamenata korištene su mješavine dronedaron-hidroklorida, poli(etilen-glikola) te komercijalnog PVA-filamenta u različitim omjerima. Mješavine su pripremljene na dva načina – kao praškasta mješavina i čvrsta disperzija. Provedena je termogravimetrijska analiza te su određena toplinska svojstva komponenata i mješavina tehnikom razlikovne pretražne kalorimetrije. Filamenti su pripremljeni ekstrudiranjem taljenjem pri 170 °C, izmjeren im je promjer te je proveden test bubrenja. Pripremljeni filamenti korišteni su za 3D-tiskanje tableta postupkom taložnog srašćivanja. Provedeno je ispitivanje in vitro oslobađanja DNR-a iz dobivenih tableta. Udio dronedarona u filamentima i tabletama određen je UV/Vis spektrofotometrijom. Rezultati ukazuju da mješavina pripremljena iz čvrste disperzije koja sadrži 10 % PEG-a ima najveći indeks tečenja taline. Filament pripremljen iz čvrste disperzije koja sadrži 10 % PEG-a pokazuje najmanja odstupanja od ciljanog promjera filamenta (1,75 mm) te je najpravilnije strukture. Tableta tiskana iz prethodno navedenog filamenta pokazuje najmanja odstupanja od ciljanog sadržaja djelatne tvari, kompaktne je strukture, što doprinosi ujednačenom otapanju, odnosno in vitro oslobađanju djelatne tvari tijekom 24 sata. Zaključno, prema svim praćenim svojstvima, pokazalo se da je mješavina koja sadrži 10 % PEG-a, 10 % DNR-a i 80 % PVA-filamenta najpogodnija za proces ekstrudiranja te 3D-tiskanja tableta.

Abstract (english)

With the increase of medical knowledge and the development of the pharmaceutical market, a need to turn medical production to a patient has emerged. The 3D printer has enabled the production of new personalized dosage forms. The development of such dosage forms requires the development of filaments containing the active pharmaceutical ingredient (API). Therefore, the aim of this paper is to prepare filaments containing dronedarone hydrochloride, an active pharmaceutical ingredient for the treatment of cardiac arrhythmia, and to enable 3D printing of tablets. Mixtures of dronedarone hydrochloride, poly(ethylene glycol) and PVA filament in various proportions were used. The mixtures are prepared in two ways – as a mixture of powder and as a solid dispersion. Thermogravimetric analysis was conducted and the thermal properties of components and mixtures were tested by differential scanning calorimetry. The filaments were prepared by hot melt extrusion at 170 °C, their diameter was measured and a swelling test was performed. Prepared filaments were used for 3D printing of tablets by Fused Deposition Modeling. An in vitro drug release assay was performed from the obtained tablets. Content of dronedarone in filaments and tablets was determined using UV/Vis spectrophotometry. The results indicate that the 10 % PEG-containing solid dispersion mixture has the highest melt flow rate. The filament prepared from a solid dispersion containing 10 % PEG has the most straightforward structure; it shows the slightest deviation from the target filament diameter (1.75 mm). The compact structure of the tablet obtained from the filament contributes to a uniform in vitro release of the DNR from matrix during 24 h. It also shows the slightest deviation from the targeted DNR content in the tablet. To conclude, the paper has demonstrated that, according to all observed properties, a blend containing 10% PEG, 10% DNR and 80% PVA filaments is most appropriate for extrusion and tablet printing.

• Keywords: filament; tableta; 3D-tiskanje (FDM); dronedaron-hidroklorid; ekstrudiranje taljenjem; in vitro oslobađanje djelatne tvari
• Keywords (english): filament; tablet; 3D printing (FDM); dronedarone hydrochloride; hot melt extrusion; in vitro drug dissolution test
• Language: croatian
• URN:NBN: urn:nbn:hr:149:389230
• Study programme: Title: Materials Science and Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-06-04 11:49:23