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Application of design of experiments in developing a sprayable gel formulation for dermal melatonin delivery
No full textMelatonin je neurohormon koji se već dugi niz godina koristi u liječenju nesanice, a novija
istraživanja pokazuju njegov veliki potencijal u liječenju kožnih oboljenja poput atopijskog
dermatitisa, vitiliga i psorijaze. Lokalnom primjenom moguće je ostvariti veću koncentraciju lijeka
na mjestu primjene te smanjiti rizik od sistemskih nuspojava. Gel kao farmaceutski oblik osigurava
dulji kontakt s kožom i bolju (bio)raspoloživost djelatne tvari. Primjena formulacije raspršivanjem
omogućava jednostavnost primjene, obuhvaćanje većih površina te ravnomjernu raspodjelu
sadržaja. Cilj ovog rada bio je razviti gel Carbopola i poletilenglikola (PEG-a) za dermalnu primjenu
melatonina raspršivanjem. Za ispitivanje utjecaja koncentracije Carbopola i PEG-a na ključna
svojstva gela te optimizaciju formulacije, primijenjen je statistički dizajn eksperimenta. Temeljem
opsežne reološke i teksturne karaterizacije te ispitivanja ujednačenosti doziranja, odabrane su
optimalne koncentracije Carbopola i PEG-a (redom 0,1 % i 5 %; m/m) za daljnju karakterizaciju i
uklapanje melatonina. Dodatak melatonina neznatno je utjecao na svojstva formulacije, što ukazuje
na prikladnost razvijenog gela za uklapanje djelatne tvari. Ispitivanjem reoloških i fizičko-kemijskih
svojstava formulacije nakon 30 dana, potvrđena je stabilnost formulacije tijekom skladištenja.
Dobiveni rezultati ukazuju na potencijal razvijenog gela s Carbopolom i PEG-om kao farmaceutskog
oblika za dermalnu primjenu melatonina raspršivanjem.Melatonin is a neurohormone commonly used for the treatment of insomnia. Recent research shows
its great potential in treating skin conditions such as atopic dermatitis, vitiligo, and psoriasis. Topical
application allows for a higher concentration of the drug at the site of application and reduces the
risk of systemic side effects. Gel as a drug delivery system ensures prolonged contact with the skin
and better (bio)availability of the drug. Application of the formulation by spraying allows for ease
of use, coverage of larger areas, and even distribution of the contents.The aim of this work was to
develop a sprayable Carbopol and polyethylene glycol (PEG)-based gel for dermal application of
melatonin. To examine the influence of Carbopol and PEG concentration on key properties of the
gel and to optimize the formulation, a statistical design of experiments was employed. Based on the
extensive rheological and textural characterization and dosing uniformity testing, the optimal
concentrations of Carbopol and PEG (0.1% and 5%, respectively; w/w) were selected for further
characterization and incorporation of melatonin. The addition of melatonin had a negligible effect
on the formulation properties, indicating the suitability of the developed gel for incorporating this
active substance. Examination of the rheological and physicochemical properties of the formulation
after 30 days confirmed the stability of the formulation during storage. The obtained results indicate
the potential of the developed Carbopol/PEG gel as a delivery system for dermal application of
melatonin by spraying
Advantages and disadvantages of purchasing over-the-counter medications
No full textOvaj rad istražuje dostupnost bezreceptnih lijekova u maloprodajnim kanalima u Hrvatskoj i svijetu te faktore koji utječu na njihovu prodaju. U današnje vrijeme prodaja bezreceptnih lijekova izvan ljekarni postala je sve češća pojava. Teorijski dio temelji se na analizi dostupne literature, stručnih članaka i časopisa o dostupnosti bezreceptnih lijekova u različitim maloprodajnim kanalima, nakon čega slijedi detaljna analiza faktora koji utječu na njihovu kupnju. Nadalje, analizira se tržište bezreceptnih lijekova s naglaskom na različite maloprodajne kanale. Cilj istraživanja je utvrditi koji čimbenici utječu na kupovinu bezreceptnih lijekova te zaključiti koje su prednosti, a koji nedostaci. Rezultati istraživanja pokazuju kako ispitanici najčešće kupuju bezreceptne lijekove u ljekarnama, dok u drugim maloprodajnim kanalima ta potrošnja je znatno manja.This paper examines the availability of over-the-counter (OTC) medicines in retail channels in Croatia and other countries, as well as the factors influencing their sales. Nowadays, the sale of OTC medicines outside pharmacies has become an increasing trend. The theoretical section is based on an analysis of available literature, expert articles and journals regarding the availability of OTC medicines in different retail channels, followed by a detailed analysis of the factors affecting their purchase. Furthermore, the paper includes an overview of the OTC medicine market, analyzing various retail channels. The research aims to identify which factors influence the purchase of OTC medicines and to determine their advantage and disadvantages. The results show that respondents still primarily buy OTC medicines in pharmacies, while they purchase them significantly less in other retail formats
Application of the design of experiments (DOE) method in the optimization of cold forming process parameters for fastener production
No full textOvaj diplomski rad bavi se optimizacijom procesa hladnog oblikovanja dvoglavih čavala u proizvodnji pričvrsnih elemenata, s posebnim naglaskom na fazu pokretanja stroja. Faza pokretanja često uzrokuje povećanu varijabilnost dimenzija i veću stopu otpada, što negativno utječe na učinkovitost i ekonomičnost proizvodnje. Cilj istraživanja je primjenom metode planiranja pokusa (Design of Experiments – DOE) identificirati ključne procesne parametre koji utječu na kvalitetu proizvoda tijekom ove faze te razviti prediktivni model za optimizaciju procesa.
U teorijskom dijelu rada obrađena je tehnologija hladnog oblikovanja metala, s posebnim osvrtom na proizvodnju pričvrsnih elemenata i izazove povezane s fazom pokretanja. Također, detaljno je prikazana metodologija planiranja pokusa (DOE) i njezina primjena u industrijskim procesima za poboljšanje kvalitete i učinkovitosti.
Eksperimentalni dio rada proveden je na stroju za hladno oblikovanje u proizvodnom pogonu. Definirani su relevantni ulazni faktori i izlazne varijable, nakon čega je provedeno planiranje i izvođenje pokusa prema odabranom DOE dizajnu. Prikupljeni podaci analizirani su statističkim metodama, uključujući ANOVA analizu i regresijsko modeliranje, kako bi se identificirali značajni utjecaji i međudjelovanja faktora.
Rezultati istraživanja omogućili su razvoj prediktivnog modela koji precizno opisuje utjecaj procesnih parametara na kvalitetu proizvoda u fazi pokretanja. Na temelju modela predložene su optimalne postavke procesa koje minimaliziraju otpad i osiguravaju stabilnu proizvodnju. Validacija modela provedena je kroz dodatne pokuse, čime je potvrđena njegova učinkovitost i primjenjivost u stvarnim proizvodnim uvjetima.This thesis focuses on the optimization of the cold forming process for double-headed nails in the production of fasteners, with a particular emphasis on the startup phase of the machine. The startup phase often leads to increased dimensional variability and higher scrap rates, which negatively affect the efficiency and cost-effectiveness of production. The objective of this study is to apply the Design of Experiments (DOE) methodology to identify key process parameters that influence product quality during this phase and to develop a predictive model for process optimization.
The theoretical part of the thesis covers the technology of cold metal forming, with a specific focus on fastener production and the challenges associated with the startup phase. Furthermore, the methodology of DOE is thoroughly explained, including its application in industrial processes to improve quality and efficiency.
The experimental work was conducted on a cold forming machine in Plant. Relevant input factors and output variables were defined, followed by the planning and execution of experiments based on the selected DOE design. The collected data were analysed using statistical methods, including ANOVA and regression modelling, to identify significant effects and interactions between factors.
The results of the study enabled the development of a predictive model that accurately describes the influence of process parameters on product quality during startup. Based on the model, optimal process settings were proposed to minimize scrap and ensure stable production. Model validation was carried out through additional trials, confirming its effectiveness and applicability in real manufacturing conditions
Fatigue life of a planetary gearbox with respect to crack initiation at the tooth root
No full textU radu je provedena numerička analiza jednostavnog planetarnog prijenosnika s tri planetarna zupčanika, pri čemu su ispitivani različiti rubni uvjeti kako bi se procijenio njihov utjecaj na raspodjelu naprezanja i zamorni vijek trajanja zuba. Geometrija zupčanika definirana je pomoću softvera KISSsoft, dok je metodom konačnih elemenata (MKE) u programskom paketu Abaqus provedena dvodimenzijska numerička analiza raspodjele naprezanja u korijenu zuba pojedinih zupčanika u prijenosniku. Na temelju dobivenih rezultata, dodatkom FE-Safe izvršena je analiza zamora primjenom principa lokalne deformacije (ε-N metoda), s ciljem određivanja potencijalnog mjesta i vremena do nastanka zamorne pukotine u korijenu zuba.In this work a numerical analysis was conducted of a simple planetary gear set with three planet gears. Different boundary conditions were investigated to assess their influence on stress distribution and tooth fatigue life. The gear geometry was defined using KISSsoft software, while a two-dimensional numerical analysis was conducted of the stress distribution at the tooth root of individual gears within the gear set using the Finite Element Method (FEM) in the Abaqus software package. Based on the obtained results, fatigue analysis was performed using FE-Safe, applying the local strain approach (ε-N method), aiming to determine the potential location and time to crack initiation at the tooth root
Arthropods as Ecto- and Endoparasites of Horses and Horse Pastures in Eastern Istria
No full textMnogi člankonošci su razvili parazitski način života, pri čemu većina predstavljaju
ektoparazite, dok su ostali endoparaziti. Konji diljem svijeta izloženi su invazijama
ektoparazitia i endoparazita uzrokojući ekonomske štete. Među mnogobrojnim vrstama
parazita konja jedne od najčešćih skupina člankonožaca koje mogu invadirati konje na
pašnjacima su krpelji, obadi i štrkovi. Stoga je cilj ovog istraživanja bio pronaći, identificirati
rod ili vrstu, spol i razvojni stadij člankonožaca te utvrditi prevalenciju pojedinih
člankonožaca na konjima ovisno o godišnjim dobima, na području dva konjička kluba istočne
Istre.
Istraživanje je provedeno od veljače 2024. do ožujka 2025. godine. Inspekcijom na
konjima i sakupljanjem iz okoliša, ukupno je sakupljeno 234 uzorka člankonožaca. Sakupljeni
su krpelji I. ricinus s udjelom od 16,88 % (26/154), D. marginatus 4,54 % (7/154) i Hy,
marginatum 78,57% (121/154) od ukupno sakupljenih krpelja. Uhvaćena su 73 obada iz
rodova Philipomyia 17,8% (13/73), Dasyrhamphis 5,47 % (4/73), dok je najbrojniji rod bila
Haematopota sa 76,71% (56/73). Od ostalih, manje prevalentnih člankonožaca, uhvaćene su
samo tri konjske kožnatice (Hippobosca equina) i četiri konjska štrka (G. intestinalis).
Temeljem dobivenih rezultata, vrsta koja predstavlja najveći rizik u prijenosu
uzročnika zaraznih i parazitarnih bolesti konja na području istočne Istre, s obzirom na
brojnost, je Hy. marginatum. Ipak, ni ostale identificirane vrste krpelja, obada i konjskih
kožnatica ne treba zanemariti zbog njihova vektorskog potencijala i negativnog utjecaja na
ponašanje i zdravstveno stanje konja.Many arthropods have developed a parasitic lifestyle, with most being ectoparasites, while
others are endoparasites. Horses worldwide are exposed to invasions by both ectoparasites
and endoparasites, causing economic losses. Among the numerous species of horse parasites,
some of the most common groups of arthropods that may infest horses on pastures include
ticks, horseflies, and botflies. Therefore, the aim of this study was to detect and identify the
genus or species, sex, and developmental stage of the arthropods, and to determine the
prevalence of specific arthropods on horses depending on the season, in the area of equestrian
riding clubs in eastern Istria.
The research was conducted from February 2024 to March 2025. Through inspection of
horses and environmental sampling, a total of 234 arthropod specimens were collected.
Among the ticks, Ixodes ricinus accounted for 16.88% (26/154), Dermacentor marginatus for
4.54% (7/154), and Hyalomma marginatum for 78.57% (121/154) of the total collected ticks.
A total of 73 horseflies were caught, belonging to the genera Philipomyia (17.8%, 13/73),
Dasyrhamphis (5.47%, 4/73), with the most numerous genus being Haematopota at 76.71%
(56/73). Among the other, less prevalent arthropods, only three forest flies (Hippobosca
equina) and four botflies (Gasterophilus intestinalis) were captured.
Based on the obtained results, the species posing the highest risk for transmission of
infectious and parasitic equine causative agents in eastern Istria, due to its abundance, is Hy.
marginatum. However, other identified species of ticks, horse flies, and forest flies should not
be overlooked due to their vector potential and negative impact on horse behavior and health
Istraživanje regulacije piruvat kinaze u kvascu Pichia pastoris i utjecaja njene overekspresije na proizvodnju antitijela
No full textThe goal of the thesis was to investigate whether the main regulatory mechanism of pyruvate kinase (Cdc19) in P. pastoris is allosteric activation by fructose-1,6-bisphosphate (FBP) as in Saccharomyces cerevisiae. To test this hypothesis, the pyruvate kinase gene (CDC19) in P. pastoris genome was substituted with mutant CDC19E397A, and strains were grown in ethanol as a carbon source. In S. cerevisiae, FBP activates pyruvate kinase (Cdc19) by interacting with the glutamate (Glu392). This regulation mechanism is important for Cdc19 inactivation in absence of glucose since it prevents futile cycling and enables gluconeogenic growth in nonfermentable carbon source. The analogous glutamate found in P. pastoris (Glu397) was replaced with alanine in a CRISPR-Cas9-mediated strategy and their growth in ethanol as a sole carbon source was determined. No differences in growth ability were observed, thus it was concluded that allosteric activation by FBP at Glu397 is not the main pyruvate kinase regulation mechanism in P. pastoris and there must be another key regulation mechanism or another interaction site important for allosteric regulation. Effects of CDC19ᴇ₃₉₇ᴀ overexpression in VHH antibody high-producing P. pastoris strain on VHH (Variable domain of the Heavy chain of the Heavychain antibody) yield were also evaluated by screening in glucose-limited conditions and results showed that CDC19ᴇ₃₉₇ᴀ overexpression can improve yield up to 2 fold.Cilj ovog rada bio je odrediti je li glavni regulacijski mehanizam piruvat kinaze u P. pastoris alosterička aktivacija pomoću frukoza-1,6-bisfosfata (FBP) kao kod Saccharomyces cerevisiae. Kako bi testirali ovu prepostavku, gen piruvat kinase (CDC19) u genomu P. pastoris je zamijenjen s CDC19E397A te su mutanti uzgajani na etanolu kao izvoru ugljika. U S. cerevisiae, FBP aktivira piruvat kinazu (Cdc19) ulazeći u interakciju s glutamatom (Glu392) te je ovaj regulatorni mehanizam važan za glukoneogeni rast na nefermentabilnim izvorima ugljika jer rezultira inaktivacijom Cdc19 te sprječava uzaludno kruženje metabolita u nedostatku glukoze. Analogni glutamat pronađen u P. pastoris (Glu397) je zamijenjen s alaninom koristeći CRISPR-Cas9 te je određivan rast mutanata na etanolu kao jedinom izvoru ugljika. Rezultati su pokazali jednak rast za mutante u usporedbi s divljim tipom iz čega se može zaljučiti da alosterička regulacija djelovanjem FBP-a na Glu397 nije glavni regulacijski mehanizam piruvat kinaze u P. pastoris te da mora postojati drugi mehanizam regulacije ili je neki drugi aminokiselinski ostatak ključan za alosteričku regulaciju Cdc19. Utjecaj overekspresije CDC19ᴇ₃₉₇ᴀ na prinos VHH antitijela u VHH proizvodnom soju P. pastoris je također ispitan u uvjetima limitacije glukozom. Rezultati su pokazali da overekspresija CDC19ᴇ₃₉₇ᴀ povećava proizvodnju VHH (Variable domain of the Heavy chain of the Heavychain antibody) prinos do 2 puta
Development of an intelligent agent based on deep learning
No full textU ovom diplomskom radu istražene su i primijenjene metode pojačanog i dubokog učenja u svrhu razvoja inteligentnog agenta sposobnog za učenje igranja videoigre kroz interakciju s okolinom. U teorijskom dijelu rada obrađeni su osnovni pojmovi pojačanog učenja (Reinforcement Learning), model Q-learning, te duboke neuronske mreže s naglaskom na konvolucijske neuronske mreže (CNN), koje su korištene zbog obrade vizualnih ulaznih podataka. U sklopu rješenja primijenjen je deep Q-network (DQN) model kao metoda učenja optimalne politike ponašanja iz vizualnog prikaza okoline.
Praktični dio rada obuhvaća razvoj simulacijskog okruženja temeljeno na jednoj od Atari igara, u kojem agent uči igranjem i prilagođava svoje ponašanje ovisno o povratnim informacijama iz okoline. Implementiran je DQN model u programskom jeziku Python, korištenjem PyCharm razvojne okoline. Razvijene su i testirane različite arhitekture neuronskih mreža, uz prilagodbu hiperparametara, dok je proces treniranja i evaluacije modela detaljno analiziran pomoću alata TensorBoard. Konačno, najbolji model pokrenut je u zasebnoj skripti za evaluaciju izvedbe agenta.This thesis explores and applies methods of reinforcement learning and deep learning with the goal of developing an intelligent agent capable of learning to play a video game through interaction with its environment. The theoretical part of the thesis covers fundamental concepts of reinforcement learning, the Q-learning algorithm, and deep neural networks, with a focus on convolutional neural networks (CNN), which were used due to their ability to process visual input data. As part of the implemented solution, the Deep Q-Network (DQN) model was used as a method for learning an optimal behavior policy based on the visual representation of the environment.
The practical part of the thesis includes the development of a simulation environment based on one of the Atari games, in which the agent learns by playing and adjusts its behavior based on feedback from the environment. The DQN model was implemented in the Python programming language using the PyCharm development environment. Various neural network architectures were developed and tested, with adjustments to hyperparameters, while the training and evaluation process was thoroughly analyzed using the TensorBoard tool. Finally, the best-performing model was executed in a separate script for agent performance evaluation
Influence of aging on the removal of poly(ethylene terephtalate) microplastics with ferrate (VI)
No full textPlastiku karakterizira visoka kemijska i fizička stabilnost, trajnost i niski troškovi proizvodnje. Zbog tih karakteristika postala je široko korištena u industriji i svakodnevnom životu. Međutim, masovna proizvodnja plastike i loše gospodarenje otpadom rezultirali su njenom sveprisutnošću u okolišu što doprinosi ekološkom problemu mikroplastike. Mikroplastika u okolišu nastaje kroz kemijsku, fizičku i biološku degradaciju, a njezina glavna obilježja uključuju visoku kemijsku stabilnost, sposobnost daljnje fragmentacije u nanoplastiku, te sposobnost adsorpcije drugih onečišćujućih tvari. Zbog potencijala za bioakumulaciju također predstavlja ozbiljan rizik za ekosustave i ljudsko zdravlje. Jedan od glavnih izvora mikroplastike u okolišu su vodeni tokovi koji su prošli sustave pročišćavanja jer se mikroplastika teško uklanja standardnim metodama pročišćavanja. Međutim, istraživanja o učinkovitosti uklanjanja mikroplastike još su u ranoj fazi zbog nemogućnosti pronalaska preciznih metoda kvantifikacije mikroplastike u okolišnim uzorcima. Ferati(VI) poznati su po svojoj multifunkcionalnosti, osobito u pročišćavanju onečišćujućih tvari, gdje zahvaljujući snažnim oksidacijskim svojstvima učinkovito djeluju na širok spektar organskih i anorganskih onečišćujućih tvari, uključujući i mikroplastiku. Poli(etilen-tereftalat) (PET) jedan je od najrasprostranjenijih plastičnih materijala, te je zbog svoje dugovječnosti i otpornosti na razgradnju jedan od glavnih tipova polimera prisutnih u okolišu u obliku mikroplastike. U ovom radu ispitana je mogućnost uklanjanja termički starene i nestarene PET mikroplastike procesom koagulacije feratima(VI) iz vodene otopine u različitim uvjetima pH. Masa istaložene mikroplastike određena je mjerenjem sadržaja organskog ugljika u filtratima uzoraka. Ferati(VI) pokazali su se donekle primjenjivim za uklanjanje mikroplastike, međutim potrebno je ispitati učinkovitost uklanjanja pri istim koncentracijama ali manjim obrocima višekratno.Plastic is characterized by high chemical and physical stability, durability, and low production costs. Due to these properties, it has become widely used in industry and daily life. However, mass production of plastic and poor waste management have led to its ubiquity in the environment, contributing to the ecological problem of microplastics. Microplastics in the environment are formed through chemical, physical, and biological degradation, and their main characteristics include high chemical stability, the ability to further fragment into nanoplastics, and the ability to adsorb other pollutants. Due to their potential for bioaccumulation, microplastics also pose a serious risk to ecosystems and human health. One of the main sources of microplastics in the environment are water bodies that have passed through treatment systems, as microplastics are difficult to remove using standard purification methods. However, research on the effectiveness of microplastic removal is still in its early stages due to the lack of precise methods for quantifying microplastics in environmental samples. Ferrates(VI) are known for their multifunctionality, especially in the treatment of pollutants, where thanks to their strong oxidative properties, they effectively act on a wide range of organic and inorganic contaminants, including microplastics. Polyethylene terephthalate (PET) is one of the most widespread plastic materials, and due to its longevity and resistance to degradation, it is one of the main types of polymers present in the environment in the form of microplastics. This study examines the possibility of removing thermally aged and pristine PET microplastics through a coagulation process with ferrates from aqueous solutions under different pH conditions. The mass of precipitated microplastics was determined by measuring the organic carbon content in the filtrates of the samples. Ferrates(VI) have shown to be somewhat effective in removing microplastics; however, it is necessary to investigate the removal efficiency at the same concentrations but with smaller, repeated doses
Synthesis and structural characterization of new quinoline-imidazole conjugates
No full textU posljednje vrijeme sve veći značaj ima primjena održivog pristupa u organskoj sintezi radi smanjenja štetnog utjecaj otapala na okoliš, energetske potrošnje te poboljšanja učinkovitosti same sinteze. U ovom radu provedena je sinteza konjugata kinolina i nitrosupstituiranog imidazola premoštenih triazolnim prstenom. U tu svrhu provedena je sinteza terminalnog alkina (15) N-propargiliranjem 4-nitro-1H-imidazola te sinteza azida (7−9) iz O-alkiliranih derivata kinolina (4−6) za dobivanje novih konjugata kinolina i imidazola (18−20). Nadalje, pripravljeni su terminalni alkini (10−12) reakcijom N-propargiliranih 4-hidroksikinolina (1−3) te imidazolnog azida (17) potrebni za sintezu novih spojeva 21−23. Također, za sintezu spojeva 24−25 provedena je sinteza 7-supstituirano kinolinskih azida (13−14) te propargiliranog imidazolnog derivata (15). Svi konačno sintetizirani spojevi u svojoj strukturi sadrže uz kinolinski, imidazolni prsten i 1,2,3-triazolni prsten. Sinteza konačnih spojeva provedena je mehanokemijskim putem, kako bi se skratilo vrijeme reakcije i poboljšalo iskorištenje. Mehanokemijska reakcija 1,3-dipolarne cikloadicije provedena je uz bakrov(II) acetat te malu količinu metanola koja je imala funkciju reducensa. Strukture svih novosintetiziranih spojeva 18−25 potvrđene su spektroskopijom 1H i 13C NMR.Recently, sustainable approach in organic synthesis has been increasingly applied to reduce the harmful impact of solvents on the environment, lower energy consumption and improve the efficiency of the synthesis itself. In this work, the synthesis of a terminal alkyne (15) was carried out via N-propargylation of 4-nitro-1H-imidazole and the synthesis of azides (7–9) from O-alkylated quinoline derivatives (4–6) to obtain new quinoline–imidazole conjugates (18–20). Furthermore, reactions of terminal alkynes (10–12), N-propargylated 4-hydroxyquinolines (1–3) and N-alkylated imidazole azide (17) afforded new compounds 21–23. For the synthesis of compounds with both quinoline and imidazole rings (24–25), quinoline azides (13–14) substituted at the C-7 position and a terminal alkyne as an imidazole derivative (15) were synthesized. All target compounds synthesized contain, in addition to quinoline, imidazole ring, and 1,2,3-triazole unit. The 1,3-dipolar cycloaddition were carried out by mechanochemical reactions using copper(II) acetate as catalyst, and a small amount of methanol, which acted as a reducing agent to convert copper(II) into catalytically active copper(I). The structures of all newly synthesized compounds 18–25 were confirmed using 1H and 13C NMR spectroscopy
Characterization methods for in situ forming hydrogels applied in extended release drug delivery systems
No full textHidrogelovi su hidrofilne, trodimenzionalne polimerne mreže koje mogu apsorbirati velike količine vode ili bioloških tekućina. Zbog visokog sadržaja vode i fizikalno-kemijske sličnosti s izvanstaničnim matriksom, ovi materijali posjeduju svojstva poput bubrenja i odlikuju se izrazitom biokompatibilnošću. U ovom radu, fokus je na poli(laktid-ko-glikolid) (PLGA) polimerima, koji su biorazgradivi i biokompatibilni kopolimeri mliječne i glikolne kiseline, široko prihvaćeni u farmaceutskim i medicinskim proizvodima. PLGA hidrogelovi su jedni od kandidata za primjenu u sustavima za dostavu lijeka s produljenim oslobađanjem u farmaceutskoj industriji. Cilj ovog završnog rada bio je istražiti metode karakterizacije in situ formiranih hidrogelova na osnovi PLGA polimera. Eksperimentalni dio obuhvaća pripravu hidrogelova koristeći polimerne otopine PLGA kopolimera s različitim molnim omjerom laktida (LA) i glikolida (GA) (LA:GA = 85:15 i 50:50) koristeći dimetil sulfoksid (DMSO) i N-metil pirolidon (NMP) kao biokompatibilna otapala u vodenom mediju (fosfatnom puferu). Provedena je karakterizacija formiranih hidrogelova kroz vrijeme gravimetrijskim testom praćenja promjene mase (bubrenje i fizikalna stabilnost), kinetike izlaska otapala tekućinskom kromatografijom visoke djelotvornosti (HPLC), promjene molekulskih masa polimera uslijed hidrolitičke razgradnje gel permeacijskom kromatografijom (GPC metodom) te morfološka ispitivanja pretražnim elektronskim mikroskopom (ESEM). Iz rezultata provedenih mjerenja vidljivo je kontinuirano smanjenje mase formiranih hidrogelova tijekom 14 dana s najvećim padom u prva 24 sata. Gravimetrijski je pokazano da se polimerima s manjim udjelom laktida masa brže smanjuje u odnosu na polimere s većim LA:GA omjerom. HPLC analiza potvrdila je izlazak DMSO otapala iz hidrogelova unutar prva 4 sata. GPC analiza pokazala je kemijsku razgradnju PLGA polimera kroz vrijeme, pri čemu se PLGA polimer s LA:GA omjerom 50:50 brže razgrađivao u odnosu na PLGA polimer s 85:15 omjerom. ESEM ispitivanja ukazala su na neke morfološke razlike između formiranih PLGA hidrogelova s obzirom na sastav polimera i vrstu otapala.Hydrogels are hydrophilic, three-dimensional polymer networks that can absorb large amounts of water or biological fluids. Due to their high water content and physicochemical similarity to the extracellular matrix, these materials possess properties such as swelling and are characterized by excellent biocompatibility. In this paper, the focus is on poly(lactide-co-glycolide) (PLGA) polymers, which are biodegradable and biocompatible copolymers of lactic and glycolic acids, widely accepted in pharmaceutical and medical products. PLGA hydrogels are one of the candidates for application in sustained-release drug delivery systems in the pharmaceutical industry. The aim of this thesis was to investigate methods for the characterization of in situ formed hydrogels based on PLGA polymers. The experimental part includes the preparation of hydrogels using polymer solutions of PLGA copolymers with different molar ratios of lactide (LA) and glycolide (GA) (LA:GA = 85:15 and 50:50) using dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) as biocompatible solvents in an aqueous medium (phosphate buffer). The formed hydrogels were characterized over time by gravimetric tests monitoring mass changes (swelling and physical stability), solvent release kinetics by high-performance liquid chromatography (HPLC), changes in polymer molecular weights due to hydrolytic degradation by gel permeation chromatography (GPC), and morphological examinations by scanning electron microscopy (ESEM). The results of the measurements showed a continuous decrease in the mass of the formed hydrogels over 14 days, with the largest decrease in the first 24 hours. Gravimetrically, it was shown that the polymer composition (LA:GA ratio) has a greater influence on the mass reduction than the type of solvent (DMSO and NMP). HPLC analysis confirmed the release of DMSO solvent from the hydrogels within the first 4 hours. GPC analysis showed chemical degradation of PLGA polymers over time, with the PLGA polymer with a LA:GA ratio of 50:50 degrading faster than the PLGA polymer with a ratio of 85:15. ESEM examinations indicated some morphological differences between the formed PLGA hydrogels with respect to on the polymer composition and the type of solvent