Naslov
Physico-chemical measurements as a prerequisite for optimization of Omeprazole synthesis

Autori
Bregović, Nikola ; Vojčić, Nina ; Požar, Josip ; Cindro, Nikola ; Horvat, Gordan ; Meštrović, Ernest ; Tomišić, Vladislav

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
International MacroTrend Conference on Medicine, Science and Technology : Program and Conference Proceedings / - Austin (TX) : Macrojournals, 2015, 26-26

Skup
International MacroTrend Conference on Medicine, Science and Technology

Mjesto i datum
Sjedinjene Američke Države, 28.12.2015. - 29.12.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
omeprazole ; optimization ; pK ; potentiometry ; calorimetry
(omeprazole ; synthesis optimization ; pK ; potentiometry ; calorimetry ;)

Sažetak
Omeprazole is a member of the proton pump inhibitor family of drugs, extensively used in treatment of peptic ulcer, gastroesophageal reflux disease and Zollinger–Ellison syndrome. The fact that it is one of the drugs indexed in the World Health Organization's List of Essential Medicines points out the importance of enhancing the synthetic procedure used in the production of this pharmaceutic. In this work we present the results of thermodynamic and kinetic studies which served as a guide in the optimization of the synthetic procedure. One of the steps in the synthesis of Omeprazole is the condensation of OMP-Cl and MTX in a mixture of methanol and water, which involves reaction of deprotonated forms of these compounds. This indicates that the protonation equilibria have a significant impact on the condensation reaction. The medium in which the reaction takes place is one of the key factors affecting the protonation properties of the reactants. Therefore, the equilibrium protonation constants of the reactants (OMP-Cl and MTX) were determined at 25 °C by means of spectrophotometric-potentiometric titrations in the mixed solvent commonly used in the synthesis of Omeprazole and in pure methanol. A significant decrease in the protonation constants with increase of water volume fraction was observed suggesting that the use of solvent with higher water content could enhance the yield of the reaction product and possibly reduce the time needed for the synthesis. In order to gain a detailed insight into the kinetics of the first step in the Omeprazole synthesis, kinetic measurements were undertaken. Kinetics of the reaction of OMP-Cl with MTX was studied in the solution of NaOH in methanol/water mixture by means of stopped-flow spectrophotometry at 25 °C. At the experimental conditions applied, MTX is almost completely present as thiolate anion whereas OMP-Cl is in the neutral form. The reaction is of second order, first with respect to both reactants. There was no significant effect of solution pH on the reaction kinetics in the range of NaOH concentration studied (0.05–0.2 mol dm–3). Further on, the reaction enthalpies of OMP-Cl and MTX protonation were determined at 25 °C by calorimetric measurements. These values enabled estimation of the temperature effect on the protonation properties of the reactants and evaluation of the heat effects of these processes in the course of synthesis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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