Fizikalno-kemijska karakterizacija omeprazola i njegovih soli

doctoral thesis

• Title (english): Physico-chemical characterization of omeprazole and its salts
• Author: Tomislav Vrbanec
• Mentor: Jože Grdadolnik (mentor); strani drzavljanin: Nije dostupno
• Committee member: Vladimir Stilinović (predsjednik povjerenstva)
• Committee member: Jože Grdadolnik (član povjerenstva); strani drzavljanin: Nije dostupno
• Committee member: Vlasta Mohaček-Grošev (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2017-12-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

U razvoju lijekova važno je izabrati najprimjereniju kristalnu formu aktivne tvari. Tvari, koje
su stabilne samo u određenom pH području, predstavljaju izazov za razvoj formulacije.
Istraživana molekula omeprazol spada u skupinu prazola; lijekova koji su inhibitori protonske
pumpe u ljudskom organizmu, a njihovo je glavno obilježje snažno i dugotrajno smanjenje
stvaranja želučane kiseline. Za prazole je poznato, da su osjetljivi na degradaciju u kiselom
okruženju. Zato se u formulaciji stabiliziraju alkalnim dodacima ili se daju u obliku bazičnih
soli. Priprava i karakterizacija bazičnih soli je potrebna u slučaju izravne uporabe u
formulaciji, odnosno i za praćenje mogućeg zasoljavanja slobodne molekule. Za potrebe
istraživanja sintetizirane su soli omeprazola iz skupine alkalijskih (Li, Na, K) i
zemnoalkalijskih metala (Mg, Ca). Istražena su i fizikalno-kemijska svojstva pet soli,
koristeći neke analitičke metode (Ramanovu i Fourier-transformiranu infracrvenu
mikroskopiju, analizu na termopostolju, dinamičku sorpciju vlage, nuklearnu magnetsku
rezonanciju, difrakciju rentgenskih zraka na polikristalnom uzorku, termogravimetriju,
diferencijalnu pretražnu kalorimetriju te teorijski izračun vibracijskih frekvencija). Zaključeno
je, da je vibracijska spektroskopija prikladna spektroskopska metoda, koja na točan, brz i
nedestruktivan način određuje fizikalno-kemijske karakteristike omeprazola i njegovih soli.

Abstract (english)

In drug development, it is important to have a suitable crystalline form of the active
substance. Substances that are stable only within a certain pH range are a challenge for the
formulation developement. Omeprazole molecule belongs to the group of prazoles; drugs
which are proton pump inhibitors in the human body, but their main characteristic is a strong
and long-lasting reduction of gastric acid formation. For the prazoles, it is known to be
sensitive to degradation in an acid environment. The formulation is then stabilized with
alkaline additives or is used in the form of basic salts. Preparation and characterization of
basic salts is needed in the case of use in the formulation and to monitor any possible
salinization of free molecule. For purposes of this study, the salts of omeprazole from the
group of alkali metal (Li, Na, K) and alkaline earth metals (Mg, Ca) were synthesized. Also
the physicochemical properties of five salts were probed, using Fourier-transform infrared and
Raman microscopy, hot stage, dynamic vapour sorption, nuclear magnetic resonance,
thermogravimetry, diffferenctial scanning calorimetry and theoretical calculation of
vibrational frequencies. It was found, that vibrational spectroscopy serves as appropriate
spectroscopic tool which in accurate, quick and non-destructive way determines the physicochemical
characteristics of omeprazole and its salts.

• Keywords: asignacija karakterističnih vrpci; fizikalna karakterizacija; mikrospektroskopija; soli omeprazola; spektroskopska karakterizacija; vibracijska spektroskopija
• Keywords (english): characteristic bands assignation; microspectroscopy; omeprazole salts; physical characterization; spectroscopic characterisation; vibrational spectroscopy
• Language: croatian
• URN:NBN: urn:nbn:hr:217:643206
• 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: 132 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-01-12 09:55:41