Odabir sustava za provedbu sferične kristalizacije

master's thesis

• Title (english): Selection of a system for spherical crystallization
• Author: Ivan Vučić
• Mentor: Jasna Prlić Kardum (mentor)
• Committee member: Jasna Prlić Kardum (predsjednik povjerenstva)
• Committee member: Aleksandra Sander (član povjerenstva)
• Committee member: Lidija Furač (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2024-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Kristalizacija je jedan od najvažnijih procesa u farmaceutskoj industriji budući da se većina djelatnih tvari proizvodi u kristalnom obliku. Sferičnom kristalizacijom omogućava se istodobno odvijanje kristalizacije i aglomeracije što rezultira formiranjem kristalnih sfernih oblika koji se mogu direktno tabletirati što pogoduje smanjenju broja koraka pri formulaciji lijeka. Ceritinib je djelatna tvar lijeka Zykadia® koji se koristi za liječenje odraslih osoba s metastatskim karcinomom pluća te prema BCS klasifikaciji djelatnih tvari spada u IV. skupinu. Svrha ovoga rada bila je pronaći optimalan sustav otapala i metodu za dobivanje sferičnih kristala ceritiniba te ispitat njihov utjecaj na oblik i strukturu kristala. Preliminarnim istraživanjima određeno je s kojim otapalima, antiotapalima, kapljevinama za premošćivanje i aditivima te u kojim omjerima će se provoditi sferična kristalizacija. Provedene su tri metode sferične kristalizacije, osim klasične sferične aglomeracije i kvazi-emulzijske difuzije otapala isprobana je i kombinacija ovih dvaju metoda. Kao najuspješniji sustav za provedbu sferične aglomeracije pokazao se THF-voda-heptan, za provedbu QESD-a THF-voda-PVP, a za kombiniranu metodu sustav THF-voda-heptan-PVP. Dobivenim sferičnim kristalima ispitana je morfologija putem optičkog mikroskopa kao i njihova struktura metodom rendgenske difrakcije.

Abstract (english)

Crystallization is one of the most important processes in the pharmaceutical industry since most active substances are produced in crystalline form. Spherical crystallization allows for the simultaneous development of crystallization and agglomeration, resulting in the generation of crystalline spherical forms that can be directly tableted, minimizing the number of steps in the drug formulation process. Ceritinib is the active substance of the drug Zykadia®, which is used for the treatment of adults with metastatic lung cancer. According to the BCS classification of active substances, it belongs to the IV. group. The purpose of this work was to find an optimal solvent system and method for obtaining ceritinib spherical crystals and to examine their influence on the size, shape, and structure of the crystals. Preliminary research has determined with which solvents, antisolvents, bridging liquids, and additives and in what proportions spherical crystallization will be carried out. Three methods were implemented, in addition to classical spherical agglomeration and quasi-emulsion diffusion of solvents. A combination of these two methods was also tried.
The THF-water-heptane system has been shown to be the most successful for spherical aglomeration, the THF-water-PVP for QESD, and the THF-water-heptane-PVP for a combination of methods. The obtained spherical crystals were examined for their morphology using an optical microscope as well as their structure using the X-ray diffraction method.

• Keywords: kristalizacija; sferični kristali; ceritinib; sustav otapala
• Keywords (english): crystallization; spherical crystals; ceritinib; solvent system
• Language: croatian
• URN:NBN: urn:nbn:hr:149:182410
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra inženjer/inženjerka kemijskog inženjerstva (sveučilišni/a magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-02-29 11:06:13