Utjecaj procesnih parametara na granulometrijska svojstva sferičnih kristala

master's thesis

• Title (english): The influence of process parameters on the granulometric properties of spherical crystals
• Author: Mirta Sabol
• Mentor: Jasna Prlić Kardum (mentor)
• Committee member: Jasna Prlić Kardum (predsjednik povjerenstva)
• Committee member: Ernest Meštrović (član povjerenstva)
• Committee member: Željka Ujević Andrijić (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

Formulacija lijekova postaje sve izazovniji proces unutar farmaceutske industrije zbog otkrivanja djelatnih tvari nepoželjnih fizikalno-kemijskih i biofarmaceutskih svojstava. Procesom sferične kristalizacije moguće je dobiti kristale djelatne tvari sferičnog oblika koji pokazuju bolja fizikalno-kemijska i biofarmaceutska svojstva te je s takvim kristalima lakše rukovati u usporedbi s kristalima koji nisu sferičnog oblika. Ovim radom ispitan je utjecaj volumnog udjela otapala, antiotapala i kapljevine za premoštenje u sustavu za provedbu sferične kristalizacije na granulometrijska svojstva kristala ceritiniba, lijeka koji se koristi za liječenje uznapredovalog raka pluća nemalih stanica i koji pripada IV razredu BCS-a. Kristali su karakterizirani stereomikroskopom i pretražnim elektronskim mikroskopom te je određena raspodjela veličina čestica i zaobljenost kristala. Metoda dizajna eksperimenta za proces sferične kristalizacije provedena je u softverskom programu Design Expert, gdje je dobiven model koji najbolje opisuje utjecaj volumnog udjela svakog otapala u sustavu za provedbu sferične kristalizacije ceritiniba na zaobljenost kristala. Utvrđeno je da u sustavu otapala za sferičnu kristalizaciju ceritiniba pri niskom udjelu otapala prema kapljevini za premoštenje neće nastati kristali sferičnog oblika, kao ni kod jako niskog udjela otapala u odnosu na antiotapalo. Optimizacijom procesa u Design Expertu dobiveni su sferični kristali najveće zaobljenosti od svih provedenih eksperimenta koja iznosi 0,91 što ukazuje na uspješno dizajniranje, modeliranje i optimiziranje sustava otapala za sferičnu kristalizaciju ceritiniba.

Abstract (english)

Drug formulation is becoming an increasingly challenging process within the pharmaceutical industry due to the discovery of active pharmaceutical ingredients with undesirable physicochemical and biopharmaceutical properties. Through the process of spherical crystallization, it is possible to obtain crystals of the active pharmaceutical ingredient with a spherical shape, which exhibit improved physicochemical and biopharmaceutical properties, and such crystals are easier to handle compared to non-spherical crystals. This thesis investigated the influence of the volume fraction of solvent, antisolvent, and bridging liquid in the spherical crystallization system on the granulometric properties of ceritinib crystals. Ceritinib is classified as a BCS class IV drug and is used for the treatment of advanced
non-small cell lung cancer. The crystals were characterized using a stereomicroscope and a scanning electron microscope, and the particle size distribution and roundness of the crystals were determined. The design of the experiment for the spherical crystallization process was conducted using the Design Expert software, where a model that best describes the influence of the volume fraction of each solvent in the system on the roundness of ceritinib crystals was developed. It was found that in the spherical crystallization system of ceritinib, spherical crystals do not form well at a low solvent-to-bridging liquid ratio, nor at a very low solvent-to-antisolvent ratio. By optimizing the process in Design Expert, spherical crystals with the highest roundness value of 0.91 were obtained, indicating successful design, modeling, and optimization of the process.

• Keywords: ceritinib; dizajn eksperimenta; granulometrijska svojstva kristala; sferična kristalizacija
• Keywords (english): ceritinib; design of experiments; granulometric properties of crystals; spherical crystallization
• Language: croatian
• URN:NBN: urn:nbn:hr:149:281322
• 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 15:15:36