Razvoj in vrednotenje nanovlaken z vgrajenimi lipidi in slabo vodotopno zdravilno učinkovino

Fajt, Patricija (avtor), Kocbek, Petra (mentor), Potrč, Tanja (komentor)

Mnogo na novo odkritih potencialnih zdravilnih učinkovin ima kljub dobremu terapevtskemu potencialu slabo vodotopnost, zato se razvoj zdravil s takimi učinkovinami pogosto zelo hitro konča. V kolikor tovrstnim učinkovinam uspemo izboljšati topnost in/ali hitrost raztapljanja, postanejo zanimive za nadaljnji razvoj. Glavni namen magistrske naloge je bil povečati hitrost raztapljanja in topnost karvedilola z vgrajevanjem v hidrofilna polimerna nanovlakna. Kot osnovno polimerno ogrodje nanovlaken smo uporabili polietilenoksid in poloksamer 407, nato pa smo v ogrodje vključili še izbrane lipide (mangovo, kakavovo ali makadamijevo maslo) ter karvedilol. Izdelana nanovlakna so bila enakomerne debeline, naključno razporejena, z gladko površino in brez por v strukturi. Ugotovili smo, da dodatek lipida, vrsta lipida in vsebnost učinkovine ne vplivajo na hitrost sproščanja karvedilola, saj se je učinkovina iz vseh izdelanih nanovlaken sprostila v 10 minutah. Proučili smo tudi topnost same učinkovine, učinkovine v fizikalni zmesi ter vgrajene v polimerna nanovlakna. Ugotovili smo, da so ravnotežne topnosti same učinkovine, učinkovine vgrajene v nanovlakna in učinkovine v fizikalni zmesi podobne. Pri raztapljanju nanovlaken smo opazili, da nastane prenasičena raztopina, ki ni stabilna, saj se karvedilol po dveh urah obori in tako sistem preide v ravnotežno stanje. Eden izmed razlogov za nastanek stanja prenasičenja je lahko amorfna oblika karvedilola v nanovlaknih. Med procesom elektrostatskega sukanja se lahko učinkovina vgradi v polimerno ogrodje v amorfni obliki, kar smo preverjali z metodo diferenčne dinamične kalorimetrije. Odsotnost ostrega endotermnega vrha pri  120 °C lahko nakazuje odsotnost kristalne oblike učinkovine, vendar tega na podlagi dobljenih rezultatov ne moremo z gotovostjo trditi, saj se je lahko karvedilol med analizo raztopil v talini polimerov, ki imajo nižje tališče. Izvedli smo tudi infrardečo spektroskopijo s Fourierovo transformacijo, da bi preverili prisotnost interakcij med komponentami v nanovlaknih. Ugotovili smo, da v spektru izdelanih nanovlaken ni vidnega vrha pri  3300 cm-1, ki je značilen za karvedilol. Ostali vrhovi, značilni za karvedilol, so manj izraziti, prav tako ni opaznih značilnih premikov glede na položaje vrhov v spektrih posameznih snovi. Na podlagi rezultatov ne moramo z gotovostjo zaključiti, da se karvedilol v nanovlaknih nahaja v amorfni obliki in da obstajajo interakcije med posameznimi komponentami v izdelanih formulacijah. So pa rezultati naše raziskave pokazali, da smo z vgradnjo karvedilola v nanovlakna uspeli povečati tako njegovo topnost kot hitrost raztapljanja.

• Jezik: Slovenski jezik
• Ključne besede: nanovlakna, topnost, karvedilol, poloksamer 407, prenasičenje
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2020
• PID: 20.500.12556/RUL-121111
• Datum objave v RUL: 30.09.2020

FAJT, Patricija, 2020, Razvoj in vrednotenje nanovlaken z vgrajenimi lipidi in slabo vodotopno zdravilno učinkovino [na spletu]. Magistrsko delo. [Dostopano 5 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=121111

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Development and characterization of nanofibers with incorporated lipids and a poorly water-soluble drug

Izvleček

Despite the good therapeutic potential many newly discovered active pharmaceutical ingredients have poor water solubility. The development of drugs with such active ingredients is often stopped very quickly. If we manage to improve their solubility and/or dissolution rate, they become interesting for further development. The aim of this master thesis was to increase the dissolution rate and solubility of carvedilol by its incorporation into hydrophilic polymer nanofibers. Polyethylene oxide and poloxamer 407 were used as key nanofiber matrix formers. Selected lipids (mango, cocoa or macadamia butter) and carvedilol were later also incorporated in nanofibers. The produced nanofibers had uniform thickness, random distribution and smooth surface, without pores in the structure. The incorporation of lipid, the type of lipid and the percentage of the active ingredient in nanofibers did not affect the rate of carvedilol release from nanofibers, as the drug was completely released from all nanofiber formulations in 10 minutes. The solubility of pure carvedilol, it's physical mixture and polymer nanofibers were also investigated. The results revealed that equilibrium solubilities of pure drug, drug in physical mixture and drug in nanofibers are similar. Dissolution of nanofibers revealed a supersaturated solution, which was not physically stable, as carvedilol precipitation was observed in two hours. One of the reasons for the supersaturation might be the presence of amorphous carvedilol in nanofibers. During electrospinning the active ingredient can incorporate into nanofibers in amorphous form, which can be verified by the differential scanning calorimetry. The absence of a sharp endothermic peak at  120 ° C may indicate the absence of the crystalline form of carvedilol in nanofibers, but this cannot be confirmed only based on obtained results, as carvedilol may have dissolved in the melt of polymers during the analysis. Infrared spectroscopy with Fourier transformation was also performed to investigate the presence of interactions between components in nanofibers. There was no visible peak characteristic for the carvedilol in the spectrum of nanofibers at  3300 cm-1. Other peaks characteristic for carvedilol were less pronounced and there were no noticeable shifts of peaks in the spectra compared to the peak positions in the spectra of individual substances. Based on the obtained results we cannot conclude with certainity that carvedilol was incorporated in nanofibers in amorphous form and that there were interactions between the individual components in the nanofiber formulations. However, the results of our study showed that the incorporation of carvedilol into nanofibers increase its solubility and dissolution rate.

• Ključne besede: nanofibers, solubility, carvedilol, poloxamer 407, supersaturation