Kvantitativno praćenje reakcije sinteze i kristalizacije omeprazola Ramanovom spektroskopijom in-line

doctoral thesis

• Title (english): Quantitative monitoring of omeprazole synthesis reaction and crystallization by in-line Raman spectroscopy
• Author: Damir Šahnić
• Mentor: Predrag Novak (mentor)
• Committee member: Snežana Miljanić (predsjednik povjerenstva)
• Committee member: Predrag Novak (član povjerenstva)
• Committee member: Ernest Meštrović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2017-09-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Opisan je razvoj kvantitativne metode praćenja reakcije sinteze i kristalizacije aktivne
farmaceutske supstance, omeprazola in situ, Ramanovom spektroskopijom in-line. Praćenje
in-line provedeno je uporabom disperzivnog Ramanovog instrumenta. Prije praćenja reakcije,
reakcijske komponente su sintetizirane i okarakterizirane off-line, pomoću Ramanove
spektroskopije i spektroskopije NMR. Spektroskopska mjerenja i komplementarne
kromatografske analize, korištene za razvoj kalibracijskog modela, prikupljene su iz seta
eksperimenata provedenih u mjerilu od jedne litre. Temeljem podataka prikupljenih tijekom
kalibracijskih eksperimenata, razvijen je kemometrijski model metodom parcijalnih projekcija
najmanjih kvadrata za sve tri reakcijske komponente, koji izračunava postotni udio svake
komponente u reakcijskoj smjesi. Metoda je uspješno primijenjena u praćenju tijeka reakcije
eksperimenta u kilo-laboratorijskom mjerilu. Kristalizacija omeprazola praćena je
semikvantitativno metodom analize glavnih komponenata i multivarijatnom rezolucijom
krivulja.

Abstract (english)

The development of a quantitative in-line Raman spectroscopic method for in situ monitoring
of the active pharmaceutical ingredient, omeprazole synthesis reaction and crystallization is
described. In-line monitoring was performed using a dispersive Raman instrument. Prior to
reaction monitoring, the reaction components were characterized off-line by means of Raman
and NMR spectroscopy. The spectroscopic measurements and the complementary
chromatographic analyses, used in the calibration model development, were gathered from a
set of experiments, performed at a one liter scale. Based on the data set obtained from the
calibration experiments, a partial least square regression model was developed for all three
reaction components, enabling the determination of the percentage of each component present
in the reaction mixture. The model was successfully applied to monitor the reaction progress
in a kilo-lab scale experiment. Omeprazole crystallization was monitored semi-quantitatively
by means of principal component analysis and multivariate curve resolution methods.

• Keywords: kvantitativno praćenje in situ; multivarijatna kalibracija; omeprazol; Ramanova spektroskopija in-line
• Keywords (english): in-line Raman spectroscopy; in situ quantitative monitoring; multivariate calibration; omeprazole
• Language: croatian
• URN:NBN: urn:nbn:hr:217:702684
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 151 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2019-09-18
• Created on: 2017-10-30 17:25:54