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New particle formation (NPF) in an urban typology
Atmosferski aerosoli definiraju se kao relativno stabilne suspenzije krutih ili tekućih čestica u plinu. Unatoč niskoj koncentraciji, njihov broj i masena koncentracija, raspodjela veličina, fizikalna svojstva i kemijski sastav vrlo su značajni. Formiranje novih čestica može značajno povećati koncentraciju kondenzacijskih jezgri oblaka u atmosferi u samo jednom danu, a na nekim mjestima dolazi do više od dvostrukog povećanja. Stoga je stvaranje novih čestica (NPF) ključno za naše razumijevanje globalne klime i trebalo bi ga uključiti u klimatske modele. Uzorkovanje se provodilo u Ljubljani te ova lokacija predstavlja urbanu pozadinsku sredinu. Za uvid u brzine rasta čestica NPF-a provedeno je izravno uzorkovanje te izravno prikupljeni podaci su izanalizirani već postojećim algoritmima i matematičkim pristupima na instrumentima: Spektrometar za brojanje submikronskih čestica (SMPS, engl. Scanning mobility particle sizer) i etalometar (AEE33). Za neizravno uzorkovanje koristio se kaskadni impaktor (engl. Berner impactor) i PM2.5 uzorkivač (engl. PM sampler). Kemijska analiza uključivala je različite kromatografske metode (ionsku kromatografiju, tekućinsku kromatografiju visoke učinkovitosti s UV/VIS ili MS detekcijom i plinsku kromatografiju s
MS detekcijom), SEM-EDS analizu i elektroanalitičke pristupe. Posebna pozornost posvećena je površinski aktivnim tvarima (SAS) i njihovoj ulozi u urbanim NPF, te identifikaciji, fizikalnoj i kemijskoj karakterizaciji 6 karakterističnih dana s različitim događajima. Analiza je ukazala na ključnu ulogu SO2, NOx, VOC, O3 u procesu formiranja čestica. Iako je uloga SO2 značajna, analize čestica su istaknule da su ugljik, kisik i dušik prevladavali u najmanjim česticama
(s promjerom do 30 nm), ističući ključnu ulogu dušikovih spojeva i VOC-a za navedene dane.Atmospheric aerosols are defined as relatively stable suspensions of solid or liquid particles in a gas. Despite their low concentration, both in terms of number and mass, as well as their size distribution, physical properties, and chemical composition, they play a significant role in atmospheric processes. The formation of new particles can significantly increase the concentration of CCN in the atmosphere in as little as a day, with some locations experiencing more than a twofold increase. Therefore, new particle formation (NPF) is crucial to our understanding of global climate and should be incorporated into climate models.
A systematic study was conducted at the urban site of Ljubljana using physical and chemical measurements (offline and online) to gain a better understanding of urban NPFFor insight into NPF physical growth rates a setup of online instrumentation was used; Scanning Mobility Particle Sizer (SMPS) and Aethalometer (AEE33). The offline setup consisting of a cascade impactor and PM sampler was used for the chemical characterization of the nucleation mode particles. The chemical analysis included different chromatographic methods (ionic chromatography, High-performance liquid chromatography with UV/VIS or MS detection, and gas chromatography with MS detection), SEM-EDS analysis and electroanalytical approaches. Special attention was given to surface-active substances (SAS) and their role in urban NPF and identification, physical and chemical characterization of 6 characteristic days with different events. The analysis indicated the key role of SO2, NOx, VOC, O3 in the process of particle formation. Although the role of SO2 is significant, particle analyzes pointed out that carbon, oxygen and nitrogen predominated in the smallest particles (up to 30 nm in diameter), highlighting the key role of nitrogen compounds and VOCs for the given days
Application of radiation in chemistry and medicine
Svrha ovog završnog rada je istražiti i objasniti ključne aspekte i primjene zračenja u poljima kemije i medicine, s posebnim fokusom na njegovu dvostruku ulogu kao neophodnog alata u znanstvenim i medicinskim istraživanjima te potencijalnih rizika za zdravlje i okoliš. Zračenje, iako je nevidljivo ljudskom oku, prisutno je u mnogim aspektima suvremenog života, od medicinske dijagnostike i terapije do kemijske analize i industrijskih procesa. U medicinskom kontekstu, zračenje se koristi za dijagnostiku bolesti putem tehnika poput rendgenskog snimanja, kao i u tretmanu određenih vrsta raka kroz radioterapiju. U kemiji, zračenje omogućuje detaljno proučavanje molekularnih struktura putem nuklearne magnetske rezonantne (NMR) spektroskopije i fluorescencije rendgenskim zrakama (XRF), što je ključno za razvoj novih materijala i lijekova. Rad također naglašava važnost sigurnosnih mjera i regulative u radu s ionizirajućim zračenjem, kako bi se zaštitilo zdravlje ljudi i okoliš. Kroz analizu znanstvenih metoda i primjena, te razmatranje etičkih i sigurnosnih implikacija, rad predstavlja zračenje kao neizostavan, no bitan dio suvremene znanosti i tehnologije.
Ovaj rad potvrđuje ključnu ulogu zračenja u napretku kemije i medicine te ističe potrebu za daljnjim istraživanjima kako bi se maksimizirale njegove koristi uz minimizaciju rizika.
Daljnji napredak u tehnologiji i metodologiji mogao bi omogućiti još preciznije i sigurnije primjene zračenja u različitim znanstvenim i medicinskim disciplinama.The purpose of this thesis is to explore and explain the key aspects and applications of radiation in the fields of chemistry and medicine, with a special focus on its dual role as an indispensable tool in scientific and medical research and potential health and environmental risks. Radiation, although invisible to the human eye, is present in many aspects of modern life, from medical diagnostics and therapy to chemical analysis and industrial processes. In a medical context, radiation is used for diagnosing diseases through techniques such as X-ray imaging, as well as in the treatment of certain types of cancer through radiotherapy. In chemistry, radiation enables the detailed study of molecular structures through nuclear magnetic resonance (NMR) spectroscopy and X-ray fluorescence (XRF) analysis, which is crucial for the development of new materials and drugs. This thesis also emphasizes the importance of safety measures and regulations in working with ionizing radiation, in order to protect human health and the environment. Through the analysis of scientific methods and applications, and consideration of ethical and safety implications, the thesis presents radiation as an indispensable, yet essential part of modern science and technology.
This thesis confirms the key role of radiation in advancing chemistry and medicine and highlights the need for further research to maximize its benefits while minimizing risks. Further advancements in technology and methodology could enable even more precise and safer applications of radiation in various scientific and medical disciplines
Polymerization of flavonoids catalysed by horseradish peroxidase
Flavoni, u koje se ubraja i apigenin, prepoznati su kao obećavajući kandidati za prevenciju metastaza raka zahvaljujući njihovoj sposobnosti inhibicije ključnih signalnih puteva. Ipak, prirodni oblik apigenina pokazuje slabu topljivost i stabilnost, što ograničava njegovu terapijsku učinkovitost. Kako bi se prevladala ta ograničenja, apigenin se može kemijski modificirati u biflavonoide i derivate poliapigenina pomoću enzima poput lakaze i peroksidaze porijeklom iz hrena (HRP). Cilj ovog rada bio je provesti polimerizaciju apigenina pomoću enzima peroksidaza porijeklom iz hrena. Polimerizacija je provedena u kotlastom reaktoru i mikroreaktoru, a tijekom procesa praćene su karakteristične veličine procesa kao što su konverzija, reakcijsko vrijeme/vrijeme zadržavanja i procesna stabilnost enzima. Oligomerna struktura flavonoida potvrđena je infracrvenom spektroskopijom s Fourierovom transformacijom (FT-IR) i kapljevinskom kromatografijom visoke djelotvornosti (HPLC-DAD). U drugom dijelu istraživanja ispitana je reakcijska kinetika polimerizacije apigenina metodom početnih brzina te su procijenjeni kinetički parametri. Kinetika polimerizacije apigenina katalizirana enzimom peroksidaza porijeklom iz hrena opisana je Michaelis–Menteničinom kinetikom. Praćenjem procesne stabilnosti enzima, primijećen je pad aktivnosti te je procijenjena konstanta deaktivacije enzima peroksidaza porijeklom iz hrena. Za reakciju provedenu u kotlastom reaktoru i mikroreaktoru postavljen je odgovarajući reaktorski model koji se sastojao od kinetičkog modela, deaktivacije enzima i bilanci tvari. Ocjena valjanosti modela provedena je na dva seta nezavisnih eksperimenata.Flavones, which include apigenin, are recognized as promising candidates for the prevention of cancer metastasis due to their ability to inhibit key signaling pathways. However,
the natural form of apigenin shows poor solubility and stability, which limits its therapeutic efficacy. To overcome these limitations, apigenin can be chemically modified into biflavonoids and polyapigenin derivatives using enzymes such as laccase and horseradish-derived peroxidase enzyme (HRP). The aim of this work was to polymerize apigenin using horseradish-derived peroxidase enzymes. The polymerization was carried out in a batch reactor and a microreactor, and during the process characteristic parameters such as conversion, reaction time/retention time and process stability of the enzyme were monitored. Oligomeric structure of flavonoids was confirmed by Fourier transform infrared spectroscopy (FT-IR) and high performance liquid chromatography (HPLC-DAD). In the second part of the study, the reaction kinetics of apigenin polymerization was investigated using the initial rate method and the kinetic parameters were estimated. The kinetics of apigenin polymerization catalyzed by the enzyme horseradish peroxidase was described by Michaelis–Menten kinetics. When monitoring the process stability of the enzyme, a decrease in activity was observed and the deactivation constant of the horseradish peroxidase enzyme was estimated. A suitable reactor model was proposed for the reaction carried out in a batch reactor and a microreactor, which consisted of a kinetic model, enzyme deactivation and a mass balance. The validation of the developed model was performed using two independent experiments
Preparation of hybrid hydrogels based on materials from biogenic sources
Ovaj rad istražuje pripravu i karakterizaciju hibridnih hidrogelova izrađenih od materijala iz biogenih izvora, s naglaskom na kombinaciju decelularizirane izvanstanične matrice (dECM) i alginata. Biomaterijali kao što su kolagen, alginat i njihovi derivati igraju ključnu ulogu u regenerativnoj medicini i tkivnom inženjerstvu zbog svoje biokompatibilnosti, sposobnosti poticanja stanične proliferacije te omogućavanja obnove tkiva. Hidrogelovi, kao trodimenzionalne umrežene strukture s visokim sadržajem vode, oponašaju prirodno tkivo te su vrlo pogodni za isporuku stanica, lijekova i drugih bioaktivnih molekula. U ovom istraživanju, hibridni hidrogelovi pripremljeni su kombiniranjem prirodnih biomaterijala s dodanim sintetskim komponentama kako bi se postigla bolja kontrola nad njihovim
fizikalno-kemijskim svojstvima. Eksperimentalni dio rada uključivao je postupak decelularizacije svinjske jetre kako bi se izolirala dECM, koja je potom modificirana metakrilacijom za bolju umreženost s drugim komponentama hidrogela. Hidrogelovi su pripravljeni u različitim omjerima dECM-MAA (metakrilirana izvanstanična matrica) i alginata, a zatim karakterizirani metodama infracrvene spektroskopije s Fourierovom transformacijom (FTIR) i razlikovne pretražne kalorimetrije (DSC). FTIR analiza pružila je uvid u kemijske strukture i međusobne interakcije unutar hibridnih hidrogelova, omogućujući identifikaciju karakterističnih kemijskih vrpci koje odgovaraju specifičnim funkcionalnim skupinama dECM-a i alginata. S druge strane, DSC analiza omogućila je procjenu termičke stabilnosti i prijelaznih temperatura hidrogelova, koje su ključne za njihovu potencijalnu primjenu u biomedicinskim uređajima. Rezultati pokazuju da je moguće manipulirati sastavom hibridnih hidrogelova kako bi se prilagodila njihova mehanička svojstva, termička stabilnost i biokompatibilnost specifičnim potrebama u biomedicinskim primjenama. Kombinacija prirodnih i sintetskih polimera, kao što su dECM-MAA i alginat, omogućuje stvaranje hibridnih materijala koji nude bolje performanse od pojedinačnih komponenata, osiguravajući bolju mehaničku otpornost i kontroliranu razgradnju. Ovi rezultati pružaju vrijedne smjernice za buduće optimizacije sastava hidrogelova u svrhu razvoja naprednih biomaterijala za regenerativnu medicinu, uključujući aplikacije kao što su isporuka lijekova, implantati i tkivni modeli. Rad također ističe važnost odabira prikladnih metoda karakterizacije, kao što su FTIR i DSC, u procjeni kompatibilnosti i stabilnosti novih biomaterijala za njihovu sigurnu i učinkovitu upotrebu.This paper investigates the preparation and characterization of hybrid hydrogels made from biogenic source materials, with a focus on the combination of decellularized extracellular matrix (dECM) and alginate. Biomaterials such as collagen, alginate, and their derivatives play a crucial role in regenerative medicine and tissue engineering due to their biocompatibility, ability to promote cell proliferation, and support tissue regeneration. Hydrogels, as three-dimensional cross-linked structures with a high water content, mimic natural tissue environments and are highly suitable for the delivery of cells, drugs, and other bioactive molecules. In this study, hybrid hydrogels were prepared by combining natural biomaterials with synthetic components to achieve better control over their physicochemical properties. The experimental part of the study involved the decellularization of porcine liver to isolate dECM, which was then methacrylated to improve cross-linking with other hydrogel components. Hydrogels were prepared in various ratios of dECM-MAA and alginate and subsequently characterized using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). FTIR analysis provided insights into the chemical structures and interactions within the hybrid hydrogels, allowing for the identification of characteristic chemical bands corresponding to specific functional groups of dECM and alginate. Meanwhile, DSC analysis enabled the evaluation of the thermal stability and transition temperatures of the hydrogels, which are critical for their potential application in biomedical devices. The results demonstrate that it is possible to manipulate the composition of hybrid hydrogels to tailor their mechanical properties, thermal stability, and biocompatibility for specific needs in biomedical applications. The combination of natural and synthetic polymers, such as dECM-MAA and alginate, allows the creation of hybrid materials that offer better performance than individual components, ensuring improved mechanical resistance and controlled degradation. These findings provide valuable guidelines for future optimization of hydrogel compositions aimed at developing advanced biomaterials for regenerative medicine, including applications such as drug delivery, implants, and tissue models. The study also highlights the importance of selecting appropriate characterization methods, such as FTIR and DSC, for assessing the compatibility and stability of new biomaterials for their safe and effective use
Temperature control in batch processes
U ovom radu provelo se ugađanje i optimiranje regulacije temperature u reaktorima s ciljem postizanja uvjeta koji omogućuju optimalno vođenje bioprocesa, što je ključno za održavanje kvalitete proizvoda i djelotvornost procesa. Regulacija temperature ima značajan utjecaj na brzinu reakcije, rast mikroorganizama, kao i na konačnu kvalitetu proizvoda u bioprocesima. U ovom radu uspoređuju se dvije metode regulacije temperature u kotlastom reaktoru pomoću električnih grijala: dvopoložajna regulacija i vremenski proporcionalna regulacija. Dvopoložajna regulacija predstavlja jednostavan način vođenja u kojemu se grijala uključuju ili isključuju, dok se vremenski proporcionalnom regulacijom omogućila finija regulacija prilagodbom vremena rada grijala s obzirom na odstupanje od zadane temperature. Provedeni su testovi na skok za analizu dinamičkog odziva sustava. Na temelju tih testova odredili su se parametri regulatora. Rezultati istraživanja daju uvid i usporedbu metoda za regulaciju temperature u bioreaktoru, s posebnim naglaskom na stabilnost sustava, brzinu postizanja zadane temperature, kao i energetsku učinkovitost.In this work, the tuning and optimisation of temperature control in reactors was carried out with the aim ofachieving optimal control of bioprocesses, which is crucial for maintaining product quality and process efficiency. Temperature control has a significant impact on reaction rate, microorganism growth and final product quality during bioprocessing.
This work compares two methods of temperature control in a boiler reactor with electric heaters: two-position control and time-proportional control. Two-position control is a simple type of control in which the heaters are switched on or off, while time-proportional control allows finer control by adjusting the heater operating time depending on the deviation from the setpoint. Step tests were carried out to analyse the dynamic response of the system.
The parameters of the controller were determined on the basis of these tests. The research results provide an insight into and a comparison of methods for bioreactor temperature control, focussing on the speed at which the setpoint temperature is reached, energy efficiency and system stability
Biocatalysis in continuous reactors
U ovom radu prikazana je primjena kontinuiranih reaktora u biokatalitičkim procesima s naglaskom na reakcije katalizirane enzimima. Kontinuirani reaktori predstavljaju održiva i ekonomski isplativa rješenja zahvaljujući mogućnosti višekratne upotrebe enzima putem tehnika imobilizacije. Imobilizacija enzima omogućuje njihovu stabilnost, jednostavno odvajanje od reakcijske smjese i ponovnu upotrebu, čime se smanjuju troškovi i povećava efikasnost. Rad daje pregled osnovnih tipova kontinuiranih reaktora kao što su reaktori s nasutim slojem katalizatora, membranski reaktori i reaktori s katalizatorima u fluidiziranom sloju. Također su prikazane metode imobilizacije enzima, uključujući adsorpciju, kovalentno vezanje, enkapsulaciju, uklapanje i umrežavanje te se opisuje kako ove metode poboljšavaju stabilnost i učinkovitost enzima. Prikazani su uspješni primjeri primjene biokatalize u kontinuiranim reaktorima, kao što su proizvodnja uridin difosfat galaktoze, sinteza kiralnih amina i bistrenje soka od naranče. Ovi primjeri pokazuju prednosti kontinuiranih procesa, uključujući smanjenje inhibicije enzima, optimizaciju uvjeta reakcije i povećanu produktivnost. U okviru rada dana je usporedba kontinuiranih reaktora s tradicionalnim kotlastim reaktorima, ističući veće konverzije, bolju stabilnost enzima i veću ukupnu učinkovitost kontinuiranih procesa.In this study, biocatalysis in continuous reactors is presented with a focus on
enzyme-catalysed reactions. Continuous reactors offer sustainable and economically viable processes thanks to the possibility of multiple use of enzymes through immobilisation techniques. Enzyme immobilisation provides stability, easy separation from the reaction mixture, and reuse, thereby reducing costs and increasing efficiency. The study provides an overview of the basic types of continuous reactors, such as packed bed reactors, membrane reactors, and fluidised bed reactors. Methods of enzyme immobilisation, including adsorption, covalent binding, encapsulation, entrapment, and cross-linking, are also presented, describing how these methods improve enzyme stability and efficiency. Successful examples of the application of biocatalysis in continuous reactors are shown, such as the production of uridine diphosphate galactose, the synthesis of chiral amines, and the clarification of orange juice. These examples demonstrate the advantages of continuous processing, including reduced enzyme inhibition, easier handling of immobilised enzymes, optimisation of reaction conditions, and increased productivity. The study also compares continuous reactors with traditional batch reactors, highlighting higher conversion rates, better enzyme stability, and higher overall efficiency of continuous processes
Synthesis, characterization and antifungal activity of new indole derivatives
Cilj ovog rada je sintetizirati i spektroskopski okarakterizirati nove derivate indola te ispitati njihovu antimikrobnu aktivnost. Sve reakcije pokazale su se uspješnima, a produkti su formirani reakcijom indola uz odgovarajuće reagense i prisutnost bakrova (II) nitrata kao katalizatora. Biološka aktivnost sintetiziranih spojeva ispitana je na mikrobnim specijama Aspergillus niger, Bacillus subtilis, Candida albicans i Pseudomonas aeruginosa koristeći metodu difuzije na pločici, pri čemu su svi spojevi pokazali potencijalnu djelotvornost.The aim of this work is to synthesize and spectroscopically characterize new indole derivatives to investigate their biological activity.. All reactions proved to be successful, and the products were formed by the reaction of indole with different reagents using copper (II) nitrate as a catalyst. The biological activity of the synthesized compounds was tested on the microbes Aspergillus niger, Bacillus subtilis, Candida albicans and Pseudomonas aeruginosa using the disk diffusion method, where all compounds showed potential effectiveness
Modification of commercial nanofiltration membranes - an overview
Primjena membranskih procesa postaje sve dominantnija u tehnologiji obrade voda, a njihov razvoj i unapređenje nužan. Ultrafiltracija i reverzna osmoza predstavljaju dobro razvijene, korištene i poznate membranske metode koje su u svakodnevnoj upotrebi, kako na industrijskoj, tako i na kućnoj razini. Nanofiltracija je relativno nova membranska metoda koja kombinira poželjne karakteristike reverzne osmoze i ultrafiltracije. Primjer je inovacije u svijetu obrade vode. Ovaj rad fokusirat će se na osnovne karakteristike navedenih membranskih procesa, njihovu primjenu i prednosti u odnosu na ostale metode. Nadalje, rad pruža uvid u klasifikaciju nanofiltracijskih membrana i njihove karakteristike. Također, obrađene su najčešće i nadolazeće metode modifikacije nanofiltracijskih membrana. Modifikacija membrana provodi se radi optimizacije samih membrana kako bi se postigle bolje ili poboljšane membranske performanse uz minimalno žrtvovanje izvornih karakteristika membrana.The application of membrane processes is becoming increasingly dominant in water treatment technology, and their development and improvement are necessary. Ultrafiltration and reverse osmosis represent well - developed, used and well - known membrane methods that are in daily use, both at the industrial and at home levels. Nanofiltration is a relatively new membrane method that combines the desirable characteristics of reverse osmosis and ultrafiltration. An example of innovation in the world of water treatment. This paper will focus on the basic characteristics of the mentioned membrane processes, their application and advantages compared to other methods. Furthermore, the work provides insight into the classification of nanofiltration membranes and their characteristics. Also, the most common and upcoming methods of modification of nanofiltration membranes are covered. Membrane modification is carried out in order to optimize the membranes themselves in order to achieve better or improved membrane performance with minimal sacrifice of the original characteristics of the membranes
Biodegradable polymer mulch films
Primjena malčeva dio je poljoprivredne prakse već desetljećima, a korištenje plastičnih malčeva naglo je poraslo u posljednjih 10 godina. Do ovog porasta dolazi zbog raznih pogodnih svojstva i sposobnosti koje plastični malčevi posjeduju, poput povećavanja temperature tla, smanjenja štetnika, očuvanja vlage u tlu, smanjenja rasta korova i mnogih drugih. Međutim, njihova upotreba nosi rizik od onečišćenja tla plastikom i mikroplastikom, te posljedično i mogućih zdravstvenih opasnosti. Iz tih razloga dolazi do razvoja biorazgradivih polimera. Glavni zahtjev za ove polimere je biorazgradivost u prirodnim klimatskim uvjetima bez proizvodnje bilo kakvih toksičnih spojeva koji zaostaju u tlu. Stoga se za izradu malčeva koriste biorazgradivi polimeri na bazi fosilnih goriva ili dobiveni iz obnovljivih izvora. Osim biorazgradivosti potrebno je dobiti malčeve visoke čvrstoće, te što lakšu dostupnost i niske cijene. Ovaj rad govori o vrstama polimera koji se mogu istraživati kao potencijalni biorazgradivi malčevi, procesu biorazgradnje malčeva, njihovim prednostima i nedostatcima, te budućim perspektivama u tom području.The application of mulches has been a part of agricultural practices for decades, and the use of plastic mulches has increased in the past 10 years. This rise is due to the various beneficial properties and capabilities that plastic mulches offer, such as increasing soil temperature, reducing pests, conserving soil moisture, suppressing weed growth, and many others. However, their use carries the risk of soil contamination with plastic and microplastics, leading to potential health hazards. Consequently, the development of biodegradable polymers has gained importance. The primary requirement for these polymers is biodegradability under natural climatic conditions without producing any toxic compounds that remain in the soil. Therefore, biodegradable polymers derived from fossil fuels or obtained from renewable sources are used in mulch production. In addition to biodegradability, it is essential to achieve high-strength mulches that are readily available and cost-effective. This paper discusses the types of polymers that can be explored as potential biodegradable mulches, the process of mulch biodegradation, their advantages and disadvantages, and future perspectives in this field
The influence of process parameters on the granulometric properties of spherical crystals
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.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