Zeljko Knez

Micronization of drugs using supercritical carbon dioxide.

Particles from gas saturated solutions, a novel method for high pressure material processing, has been used for micronization of practically insoluble calcium-channel blockers nifedipine and felodipine and the hypolipidemic agent fenofibrate with the aim of increasing their dissolution rate and hence their bioavailability. Dependent on the pre-expansion conditions, a mean particle size of between 15 and 30 microm was achieved for micronized nifedipine and 42 microm for micronized felodipine. The particle size of processed fenofibrate, on the other hand, increased due to agglomeration. The highest dissolution rate was achieved by preparation of drug coprecipitates with PEG 4000.

Improvement of nifedipine dissolution characteristics using supercritical CO2

Abstract An application of supercritical fluids (SCFs) for processing of pharmaceuticals is presented. PGSS (Particles from Gas Saturated Solutions), a novel method for high pressure material processing, has been used to improve technological characteristics of the poorly water soluble calcium antagonist nifedipine. Nifedipine was micronized with PGSS and the influence of pre-expansion conditions on the particle size was studied. With PGSS, coprecipitates of nifedipine and PEG 4000 were prepared and evaluated. The solid dispersions had enhanced dissolution rates. The PGSS process shows some advantages over classical methods for solid dispersion preparation.

HIGH PRESSURE EXTRACTION OF VITAMIN E-RICH OIL FROM SILYBUM MARIANUM

Abstract The efficiency of high pressure extraction in the production of oil with a high concentration of vitamin E, from seeds of Silybum marianum , was investigated. The solvents used in extraction were liquid or supercritical carbon dioxide and liquid propane. Operating parameters were 100, 200, 300 bar and 25, 40, 60 and 80°C for CO 2 and 60, 150, 200 bar and 40, 60 and 80°C for propane, respectively. The influence of process parameters on the total yield of extraction, vitamin E composition and acid value of the extracts was investigated. Results were compared with those obtained for conventional extraction with organic solvents (n-hexane, petroleum ether, dichloromethane, chloroform). The mathematical model based on the adsorption–desorption equilibrium of oil from solid tissue, the diffusion of oil to the surface and mass transfer through external film into the bulk, described the experimental extraction results well.

Removal of BTEX vapours from waste gas streams using silica aerogels of different hydrophobicity

Silica aerogels are alternative adsorbents to activated carbon (AC) for the removal and the recovery of organic vapours from gas streams. The adsorption capacity measurements of different silica aerogels were done by mini-column method. Continuous adsorption measurements show that silica aerogels are excellent adsorbents of BTEX vapours from waste gas stream. Compared to the most used adsorbents, such as AC and silica gel, aerogels exhibit capacities which enormously exceed that of both commonly used adsorbents. By increasing the degree of hydrophobicity, aerogels become less effective, but they do not adsorb water vapour from gas stream. Silica monolith aerogels with different degrees of hydrophobicity by incorporating methyltrimethoxysilane (MTMS) or trimethylethoxysilane (TMES) in standard sol-gel synthesis were prepared. Excellent properties of aerogels, obtained with the sol-gel synthesis, were preserved with supercritical drying with CO(2). The degree of hydrophobicity of the aerogels was tested by measuring the contact angle (theta) of a water droplet with the aerogel surface. The aerogels were also characterised by FTIR, nitrogen sorption and DSC/TG measurements.

Ionic liquids as (co)solvents for enzymatic reactions

Ionic liquids are low melting point salts that represent an exciting new class of reaction solvents. Many reactions show advantages when carried out in ionic liquids, either with regard to enhanced reaction rates, improved selectivity, or easier reuse of catalysts. To ascertain the influence of ionic liquids on the enzyme activity, three different ionic liquids 1-butyl-3-methylimidazolium chloride ([bmim] [CI]) 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] [PF6]) and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) were synthesized and investigated as potential media for the hydrolysis of carboxymethyl cellulose, catalyzed by non-immobilized cellulase from Humicola insolens (Celluzyme 0,7T) and for ester synthesis, catalyzed by immobilized lipase from Rhizomucor miehei (Lipozyme RM IM). Enzyme-catalyzed reactions were performed in a batch stirred reactor at atmospheric pressure. Celluzyme 0,7T showed better activity in hydrophobic ionic liquid ([bmim] [PF6]), as compared to hydrophilic ionic liquid ([bmim] [BF4]). In the case of Lipozyme RM IM, the synthetic activity of the enzyme was strongly reduced by incubating the enzyme in ionic liquids.

Rosemary extracts improve flow-mediated dilatation of the brachial artery and plasma PAI-1 activity in healthy young volunteers.

Polyphenol antioxidants decrease the risk of atherosclerosis. The study aimed to evaluate prospectively in healthy young participants the effect of oral rosemary extracts (RE), consisting of diphenols, upon endothelial dysfunction (ED), preceding structural atherosclerosis. Nineteen healthy young volunteers were studied prospectively, who received oral RE (77.7 mg) for 21 days, consisting of active substances carnosol (0.97 mg), carnosic (8.60 mg) and rosmarinic acid (10.30 mg). Before and after RE treatment, the study evaluated fasting serum levels of plasminogen‐activator‐inhibitor‐1 (PAI‐1), vascular cell adhesion molecule 1 (VCAM‐1), inter‐cellular adhesion molecule 1 (ICAM‐1), superoxide dismutase (SOD), glutathione peroxidase (GPX), fibrinogen, high‐sensitivity capsular reactive protein (hs‐CRP), tumor‐necrosis factor α (TNF‐α), the lipid profile and ED, characterized as flow‐mediated dilatation (FMD) in the brachial artery of <4.5%, estimated by ultrasound measurements. After 21 days, any side effects were registered, the mean FMD increased nonsignificantly (6.51 ± 5.96% vs 7.78 ± 4.56%, p = 0.546) and ED decreased significantly (66.6% vs 16.6%, p = 0.040). Among the serum markers, only the mean PAI‐1 level decreased significantly (4.25 ± 1.46 U/mL vs 3.0 ± 0.61 U/mL, p = 0.012) after 21‐day RE supplementation. It is concluded that oral RE supplementation has the potential to improve serum PAI‐1 activity and ED in young and healthy individuals. Copyright

Insights in starch acetylation in sub- and supercritical CO2.

An in-depth study on the acetylation of starch with acetic anhydride (Ac(2)O) and sodium acetate (NaOAc) as the catalyst in pressurized carbon dioxide (scCO(2)) in a broad pressure range (8-25MPa) and a temperature of 90°C is provided. Highest degrees of substitution (DS) of 0.29 (1h reaction time) and 0.62 (24h reaction time) were found near the critical point of the mixture (15MPa). The phase behavior of the system CO(2), starch and acetic anhydride (Ac(2)O) was studied in a high pressure view cell. The critical points were a clear function of the temperature and increased from the range of 9.4-10MPa to 14.5-14.8MPa when going from 50 to 90°C (Ac(2)O mole fraction at the critical point in the range of 0.08-0.09). Acetylation experiments with a range of starch particles sizes showed a clear relation between the DS and the particle size.

Fitting Sovova's mass transfer model using an evolutionary algorithm and differential evolution

In chemical engineering, reliable models are necessary to reduce the cost of process design. An evolutionary algorithm with resizable population was used to estimate coefficients of Sovovas mass transfer model and was compared with a global optimiser found in the literature and commonly used differential evolution algorithm. Comparison of the evolutionary algorithm to the global optimisation technique proved that the evolutionary algorithm is more robust, efficient, and significantly better than the global optimiser in regards to the deviation of the model from experimental data. It is also shown that the proposed evolutionary algorithm performed better than differential evolution algorithm.

Production of biogas by SCF technology

Hydrogen is expected to become an important fuel in the long-term since in combination with fuel cells it offers the opportunity of an intrinsically clean energy supply. By application of supercritical water gasification (SCWG) concept, sustainable hydrogen can be produced from biomass and waste. The paper offers an overview of some recently published papers dealing with SCWG of model compounds and a summary of the investigations on SCWG of real agricultural and food processing wastes. In the frame of our work an intense research was performed to support analyses of SCWG of glycerol and was supported by the investigation of phase equilibrium for the systems gas/water and gas mixtures/water. When glycerol/water solutions were directly injected in the reactor operating at supercritical conditions, gases with high C2+ were obtained by the reforming in supercritical water unit. To reduce the hydrocarbon concentrations and to obtain a syngas with higher CO/CO2 ratios from a mixture of gases (H2, CO, CO2 and CH4), catalytic reactions at high pressure and temperature were introduced reflecting in an increase of the content of H2 and CO. Solubility measurements were conducted for the binary systems of gas and water at elevated pressures and temperatures.

Enzyme-catalyzed reactions in different types of high-pressure enzymatic reactors

The enzyme-catalyzed hydrolysis of carboxy-methyl cellulose (CMC) was performed in three different types of reactors; in a batch stirred-tank reactor (BSTR) operating at atmospheric pressure, in a high-pressure batch stirred-tank reactor (HP BSTR) and in a high-pressure continuous tubular-membrane reactor (HP CTMR). In the high-pressure reactors aqueous SC CO2 was used as the reaction medium. The aim of our research was optimization of the reaction parameters for reaction performance. All the reactions were catalyzed by cellulase from Humicola insolens. Glucose production in the high-pressure batch stirred-tank reactor was faster than in the BSTR at atmospheric pressure. The optimal temperature for the reaction performed in the BSTR at atmospheric pressure was 30°C, while the optimal temperature for the reaction performed in SC CO2 was 32°C. The influence of the application of tubular ceramic membranes in the high-pressure reaction system was studied on the model reaction of CMC hydrolysis at atmospheric pressure and in SC CO2. The reaction was catalyzed by cellulase from Humicola insolens covalently linked to the surface of the ceramic membrane. The hydrolysis of CMC in SC CO2 and at atmospheric pressure was performed for a long time period. The reaction carried out in SC CO2 was more productive than the reaction performed at atmospheric pressure.