Određivanje optimalnih procesnih uvjeta kod razgradnje nilotinib hidroklorida

master's thesis

• Title (english): Determination of optimal process conditions for degradation of nilotinib hydrochloride
• Author: Silvija Bukvić
• Mentor: Lidija Furač (mentor)
• Committee member: Lidija Furač (predsjednik povjerenstva)
• Committee member: Matija Cvetnić (član povjerenstva)
• Committee member: Dajana Kučić Grgić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu ispitano je nekoliko značajnijih procesa razgradnje u svrhu smanjenja koncentracije farmaceutika, nilotinib hidroklorida u vodi pri različitim uvjetima. Nilotinib hidroklorid pripada skupini specifičnih inhibitora enzima tirozin kinaze, a upotrebljava se za liječenje kronične mijeloične leukemije. Korišteni postupci razgradnje su hidroliza, prisilna razgradnja oksidansom, fotoliza te fotooksidacija. Dobiveni rezultati pokazuju da je svaka od navedenih metoda pogodna za razgradnju nilotinib hidroklorida. Korištenjem agresivnijih metoda koje se temelje na UV zračenju, različitim oksidansima ili njihovim kombinacijama dobiven je veliki broj novih produkata različitih karakteristika. Za određivanje optimalnih uvjeta razgradnje nilotinib hidroklorida korištena je metoda Taguchi dizajna. Utjecaji pojedinih parametara za razgradnju, određeni su matematičkim modeliranjem. Rezultati pokazuju slab utjecaj oksidansa i pH zbog izuzetne stabilnosti molekule nilotinib hidroklorida. Uvjeti koji znatno pogoduju razgradnji nilotinib hidroklorida su visoka koncentracija kloridnih iona te kombinacija visoke koncentracije fosfata i niske koncentracije sulfata.

Abstract (english)

In this paper, several significant degradation processes were investigated in order to reduce the concentration of pharmaceuticals, nilotinib hydrochloride in water under different conditions. Nilotinib hydrochloride belongs to a group of specific tyrosine kinase enzyme inhibitors and is used to treat chronic myeloid leukemia. The decomposition methods used are hydrolysis, forced oxidative decomposition, photolysis and photooxidation. The results obtained show that each of these methods is suitable for the degradation of nilotinib hydrochloride. By using more aggressive methods based on UV radiation, different oxidants or their combinations, a large number of new products with different characteristics were obtained. The Taguchi design method was used to determine the optimal degradation conditions of nilotinib hydrochloride. The influences of individual parameters for degradation were determined by conducting mathematical modeling. The results show a weak effect of oxidants and pH due to the exceptional stability of the nilotinib hydrochloride molecule. Conditions that are significantly conducive to the degradation of nilotinib hydrochloride are high concentrations of chloride ions and a combination of high phosphate concentrations and low sulfate concentrations.

• Keywords: farmaceutik; hidroliza; prisilna razgradnja; fotoliza; fotooksidacija; Taguchi metoda; nilotinib hidroklorid
• Keywords (english): pharmaceutical; hydrolysis; forced degradation; photolysis; photooxidation; Taguchi method; nilotinib hydrochloride
• Language: croatian
• URN:NBN: urn:nbn:hr:149:512864
• Project: Number: IP-2014-09-7992; Title: Modeliranje okolišnih aspekata napredne obrade voda za razgradnju prioritetnih onečišćivala; Title: Modeling of environmental aspects of advanced water treatment for fegradation of priority pollutants; Acronym: MEAoWT; Leader: Tomislav Bolanča; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2022-02-28 18:06:35