Uvećanje procesa sferične kristalizacije

master's thesis

• Title (english): Spherical crystallization scale-up
• Author: Lana Crnac
• Mentor: Jasna Prlić Kardum (mentor)
• Committee member: Jasna Prlić Kardum (predsjednik povjerenstva)
• Committee member: Željka Ujević Andrijić (član povjerenstva)
• Committee member: Gordana Matijašić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2024-09-30, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Sferična kristalizacija metoda je kristalizacije koja rezultira izravnim nastankom sferičnih kristala poboljšanih fizikalno – kemijskih svojstava čime se olakšava proces proizvodnje lijekova. U ovome radu provedena je sferična kristalizacija djelatne tvari ceritiniba. Kristalizacija je provedena kombinacijom metoda sferične aglomeracije i kvazi – emulzijske difuzije otapala za sustav otapala u kojemu je kao dobro otapalo korišten tetrahidrofuran, kao kapljevina za premoštenje heptan te kao loše otapalo voda uz dodatak
poli(vinil – pirolidon) – a (1 % w/w). Proces kristalizacije proveden je i optimiziran u manjem kristalizatoru te su usporedbom oblika i veličina dobivenih kristala odabrani omjeri otapala za uvećanje procesa. Kao kriterij uvećanja primijenjena je kritična brzina miješanja. Minimalna brzina miješanja za postizanje stanja potpune disperzije određena je vizualno u sustavu heptan – voda, dok je minimalna brzina vrtnje miješala potrebna za postizanje stanja potpune suspenzije određena pomoću Zwieteringovog izraza. Granulometrijska svojstva kristala karakterizirana su svjetlosnim mikroskopom i čestičnim analizatorom. Usporedbom dobivenih kristala zaključuje se kako udio kapljevine za premoštenje i brzina miješanja imaju značajan utjecaj na veličinu kristala. Bolji rezultati dobiveni su pri vizualno određenoj kritičnoj brzini miješanja. Rendgenskom difrakcijskom analizom utvrđeno je kako prisutnost dodatka i kapljevine za premoštenje ne utječe na unutarnju strukturu ceritiniba.

Abstract (english)

Spherical crystallization is a method of crystallization that results in the direct formation of spherical crystals with improved physical and chemical properties, thus facilitating the process of drug production. In this paper, spherical crystallization of the active pharmaceutical ingredient ceritinib was carried out. Crystallization was carried out by a combination of spherical agglomeration and quasi – emulsion solvent diffusion methods for a solvent system in which tetrahydrofuran was used as a good solvent, heptane as a bridging liquid, and water as a poor solvent with the addition of poly – (vinyl – pyrrolidone) (1 % w/w). The crystallization process was carried out and optimized in a smaller crystallizer, and by comparing the shapes and sizes of the obtained crystals, solvent ratios were selected to scale – up the process. The critical impeller speed was applied as the scale – up criteria. The minimum impeller speed to achieve the complete dispersion was determined visually in the heptane – water system, while the minimum impeller speed required to achieve the complete suspension was determined using the Zwietering correlation. The granulometric properties of the crystals were characterized by a light microscope and a particle analyzer. By comparing the obtained crystals, it is concluded that the proportion of bridging liquid and the impeller speed have a significant influence on the size of crystals. Better results were obtained at the visually determined impeller speed. X – ray diffraction analysis determined that the presence of additives and bridging liquid does not affect the structure of ceritinib.

• Keywords: ceritinib; sferična kristalizacija; uvećanje procesa
• Keywords (english): ceritinib; spherical crystallization; scale – up
• Language: croatian
• URN:NBN: urn:nbn:hr:149:065979
• Project: Number: KK.01.1.1.07.0017; Title: Napredno vođenje procesa kristalizacije; Title: Advanced Control of Crystallization Process; Acronym: CrystAPC; Leader: Nenad Bolf; Jurisdiction: eu; Funder: Europska unija; Funding stream: European Regional Development Fund
• 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: 2024-11-11 15:48:43