Primjena niskotemperaturnih eutektičkih otapala za poboljšanje formulacije ciprofloksacina kao aktivnog farmaceutskog sastojka lijeka

master's thesis

• Title (english): Application of deep eutectic solvent for improvement of drug formulation with ciprofloxacin as an active pharmaceutical ingredient
• Author: Anamaria Šintić
• Mentor: Kristina Radošević (mentor)
• Committee member: Senka Djaković (predsjednik povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Cell Technology, Application and Biotransformations); Zagreb
• Defense date and country: 2021-12-20, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Interes znanstvenika za nove i ekološki prihvatljive pristupe u proizvodnji i formulaciji lijekova prvenstveno se odnosi na primjenu prirodnih niskotemperaturnih eutektičkih otapala (NADES) kao medija za biotehnološku pripravu ili kao sredstva za formulaciju lijeka. Cilj ovog rada bio je odabir najpogodnijeg NADES-a za razvoj formulacije antibiotika ciprofloksacina poboljšane topljivosti i permeabilnosti. Pomoću računalnog modela COSMO-RS ispitana je topljivost ciprofloksacina u velikom broju NADES-a. Najbolja topljivost predviđena je u timol:oktanska kiselina, što je potvrđeno tekućinskom kromatografijom visoke djelotvornosti. Praćena je stabilnost ciprofloksacina u referentnom otapalu i NADES-u Ty:C8 tijekom 35 dana pri različitim temperaturama. Nadalje, ispitana je in vitro biološka aktivnost formulacije ciprofloksacina i NADES-a na tumorskoj staničnoj liniji Caco- 2. Također, provedeno je ispitivanje permeabilnosti formulacije pomoću PAMPA testa propusnosti kroz umjetnu membranu. Razvojem formulacije ciprofloksacina u NADES-u Ty:C8 postignuto je poboljšanje topljivosti i permeabilnosti ciprofloksacina, uz očuvanje stabilnosti i antimikrobne aktivnosti djelatne tvari, što ukazuje na moguću farmaceutsku primjenu takve formulacije u većem mjerilu.

Abstract (english)

Scientific interest in a new and environmentally friendly approaches in development of drug formulations primarily refers to the use of natural deep eutectic solvents (NADES). The aim of this study has been the proper selection of NADES in order to develop formulation of antibiotic ciprofloxacin with improved solubility and permeability. Using a computer predictive model COSMORS, solubility of ciprofloxacin in a large number of NADES has been evaluated. The best solubility was achieved in thymol:octanoic acid, which is determinated using high performance liquid chromatography. The stability of ciprofloxacin in NADES Ty:C8 has been monitored during 35 days at different temperatures, while in vitro biological activity of the formulation was examined using cell line Caco-2. Furthermore, permeability of the formulation has been tested using PAMPA test. Synthesis of ciprofloxacin formulation in Ty:C8 improved solubility and permeability of ciprofloxacin, without affecting its stability and maintaining antimicrobial activity. Therefore, pharmaceutical application of this formulation on a large scale is possible.

• Keywords: biološka aktivnost; ciprofloksacin; permeabilnost; prirodno niskotemperaturno eutektičko otapalo; topljivost
• Keywords (english): biological activity; ciprofloxacin; deep eutectic solvents; permeability; solubility
• Language: croatian
• URN:NBN: urn:nbn:hr:159:932227
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-01-31 13:50:21