Primjena niskotemperaturnih eutektičkih otapala za poboljšanje formulacije lijeka s derivatima ciprofloksacina kao aktivnim farmaceutskim sastojkom

master's thesis

• Title (english): Application of deep eutectic solvents for improvement of drug formulation with ciprofloxacin derivatives as an active pharmaceutical ingredient
• Author: Viktorija Belavić
• 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

Cilj ovoga rada je poboljšanje topljivosti aktivnih farmaceutskih sastojaka (API) primjenom prirodnih niskotemperaturnih eutektičkih otapala (NADES) kao zelenih otapala te sinteza derivata ciprofloksacina zbog sve većeg problema antibiotičke rezistencije spram tog lijeka. Upotrebom softvera COSMOtherm predviđena je topljivost dva 7-(4-(supstituiran)piperazin-1-il) derivata ciprofloksacina u NADES-ima, pri čemu je najbolja topljivost predviđena u kiselim i hidrofobnim otapalima. UV/Vis spektrofotometrijom je eksperimentalno određena najbolja topljivost derivata u hidrofobnom NADES-u timol:kumarin (3:2) koja iznosi 10 mg mLˉ¹ za N-acetilirani i 5 mg mLˉ¹ za N-2-metilpentanoilni derivat. Stabilnost formulacija praćena je spektrofotometrijski tijekom vremena pri 4 °C i 25 °C te su derivati stabilni prvih desetak dana, nakon čega je došlo do pada stabilnosti. Testom propusnosti kroz umjetnu membranu (PAMPA) uočeno je poboljšanje propusnosti N-acetiliranog derivata u formulaciji s NADES-om, ali ne i za drugi derivat. Ispitana je biološka aktivnost otopina derivata ciprofloksacina na Caco-2 staničnoj liniji, pri čemu je primijećeno inhibitorno djelovanje na rast stanica.

Abstract (english)

The aim of this work is to improve the solubility of active pharmaceutical ingredients (API) by using natural deep eutectic solvents (NADES) as green solvents and the synthesis of ciprofloxacin derivatives due to the growing problem of antibiotic resistance. Using COSMOtherm software, the solubility of two 7-(4-(substituted)piperazine-1-yl) ciprofloxacin derivatives in NADESs was predicted, with the best solubility in acidic and hydrophobic solvents. Solubility was experimentally determined by UV/Vis spectrophotometry and the best solubility of derivatives was in the hydrophobic NADES thymol: coumarin (3:2) of 10 mg mLˉ¹ for N-acetyl and 5 mg mLv for N-2-methylpentanoyl derivative. The stability of the formulation was monitored spectrophotometrically over the time at 4 °C and 25 °C and the derivatives were stable for the first ten days, afterwards a decrease in stability was observed. The parallel artificial membrane permeability assay (PAMPA) was conducted and improvement of permeability N-acetyl derivative in the formulation with NADES was detected, but not for another derivative. The biological activity of solution of ciprofloxacin derivatives on the Caco-2 cell line was examined, and an inhibitory effect on cell growth was determined.

• Keywords: prirodna niskotemperaturna eutektička otapala; derivati ciprofloksacina; COSMOtherm; PAMPA; biološka aktivnost
• Keywords (english): natural deep eutectic solvents; ciprofloxacin derivatives; COSMOtherm; PAMPA; biological activity
• Language: croatian
• URN:NBN: urn:nbn:hr:159:681844
• 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 13:26:27