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Marijana Končič, Branka Zorc and Predrag Novak

Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymer

Two hydrosoluble conjugates of 17β-estradiol (ED) and estradiol-17β-valerate (EV) with polyaspartamide polymer were prepared and characterized. ED and EV were first chemically modified and bound to poly[α,β-(N-2-hydroxyethyl-DL-aspartamide)]-poly[α,β-(N-2-aminoethyl-DL-aspartamide)] (PAHA), a hydrosoluble polyaspartamide-type copolymer bearing both hydroxyl and amino groups. ED was first converted to 17-hemisuccinate (EDS) and then bound to PAHA. In the resulting conjugate PAHA-EDS, the estradiol moiety was linked to the polymer through a 2-aminoethylhemisuccinamide spacer. On the other hand, EV was first converted to estradiol-17β-valerate-3-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EV. In the prepared conjugate PAHA-EV, the estradiol moiety was covalently bound to the polyaspartamide backbone by carbamate linkage, through an ethylenediamine spacer. The polymer-drug conjugates were designed and prepared with the aim to increase water-solubility, bioavailability and to improve drug delivery of the lipophilic estrogen hormone.

Open access

Mario Novak, Antonija Trontel, Anita Slavica, Predrag Horvat and Božidar Šantek

Abstract

For simulations of flow and microbial conversion reactions, related to modeling of simultaneous extraction and fermentation process in a single sugar beet cossette a software package OpenFOAM was used. The mass transfer of the components (sucrose, glucose, fructose and ethanol) in the studied system was controlled by the convection and diffusion processes. Microbial conversion rates and yield coefficients were experimentally determined and/or estimated by mathematical simulation. Dimensions of the model sugar beet cossette (SBC) were: average length of cosettes 40.10 mm, average thickness 3.32 mm and average width 3.5 mm, and represented in the model as a square-shape cross-section mathematical simulation. Dimensions of the model sugar beet cossette (SBC) were: average length of cosettes 40.10 mm, average thickness 3.32 mm and average width 3.5 mm, and represented in the model as a square-shape cross-section used to study the mass transfer and microbial conversion rates on the scale of single sugar beet cossette in the short time scales (up to 25 s). This model can be used for simulation of extractant flow around single sugar beet cossette as well as for description of simultaneous extraction and fermentation process in the studied system.

Open access

Tomislav Jednačak, Aden Hodzic, Otto Scheibelhofer, Marijan Marijan, Johannes G. Khinast and Predrag Novak

Abstract

Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.