Igor Plazl

Steroid extraction in a microchannel system—mathematical modelling and experiments

The continuous ethyl acetate extraction of progesterone and 11alpha-hydroxyprogesterone, a reactant and the product of the biotransformation step involved in corticosteroid production, was studied in a microchannel at different flow velocities. In addition, non-steady state batch extraction without mixing was performed and modelled in order to verify the theoretically predicted parameters. In order to analyze experimental data and to forecast microreactor performance, a three-dimensional mathematical model with convection and diffusion terms was developed considering the velocity profile for laminar flow of two parallel phases in a microchannel at steady-state conditions. For the numerical solution of a complex equation system, non-equidistant finite differences were used. Very good agreement between model calculations and experimental data was achieved without any fitting procedure. Due to the efficient phase separation and high extraction yields obtained, the micro scale extraction units were found to be a promising tool for the development of an integrated system of 11alpha-hydroxylation of progesterone by Rhizopus nigricans in the form of pellets.

Microscale technology and biocatalytic processes: opportunities and challenges for synthesis

Despite the expanding presence of microscale technology in chemical synthesis and energy production as well as in biomedical devices and analytical and diagnostic tools, its potential in biocatalytic processes for pharmaceutical and fine chemicals, as well as related industries, has not yet been fully exploited. The aim of this review is to shed light on the strategic advantages of this promising technology for the development and realization of biocatalytic processes and subsequent product recovery steps, demonstrated with examples from the literature. Constraints, opportunities, and the future outlook for the implementation of these key green engineering methods and the role of supporting tools such as mathematical models to establish sustainable production processes are discussed.

Esterification of Benzoic Acid in Microwave Tubular Flow Reactor

Abstract Acid-catalyzed esterification of benzoic acid with ethanol was investigated in a continuous tubular flow reactor heated by microwaves. The microwave reactor operated at medium pressure and high temperature conditions. Esterification was catalyzed with sulfuric acid and with ion exchange resins. Kinetic parameters of esterification were determined in a stirred glass vessel using conventional heating. A mathematical model was proposed to describe temperature profiles and to predict the conversion of the reaction in the tubular flow microwave reactor. The calculated conversions of benzoic acid based on predicted temperature profiles agree with experimental data. The operating conditions in the microwave reactor allowed us to achieve high conversions at relatively low residence times.

The influence of β-cyclodextrin on the kinetics of progesterone transformation by Rhizopus nigricans

The process of progesterone 11α-hydroxylation by the pelleted growth form of the filamentous fungus Rhizopus nigricans has been described with a mathematical model, based on Michaelis-Menten enzyme kinetics and the rate of substrate dissolution. It was confirmed that the low water solubility of steroids is the limiting step of this process at high steroid concentrations. In order to overcome this problem, β-cyclodextrin, which is known to form inclusion complexes with these organic compounds, was added to the production medium. The phase solubility of the steroid-β-cyclodextrin system was investigated and the effect of β-cyclodextrin addition on progesterone biotransformation evaluated. Enhancement of steroid solubility was demonstrated and nearly two-fold increase in reaction rate was found in the presence of β-cyclodextrin.

Evaluation of Diffusion Coefficient Determination using a Microfluidic Device

A theoretical description of the convection-diffusion process in a homogeneous system enabling estimation of diffusion coefficients employing commercially available Y-junction microchannel is presented. A detailed numerical analysis based on finite volumes and finite differences, namely the explicit, implicit and Crank-Nicolson method, was performed and analyzed on the same domain in order to verify the proposed models. All numerical approaches provided stable solutions with certain numerical variations depending on the number of iterations defined by the mesh density. In addition, the method was validated with measurements of diffusion coefficients of some selected components in the short Y-junction microchannel. Benefits and possible pitfalls of this estimation method are discussed.

Batch and continuous transformation of progesterone by Rhizopus nigricans pellets in the presence of β-cyclodextrin

A pelleted morphological form of Rhizopus nigricans, which might be regarded as a naturally immobilized biomass, enabled development of a continuous process of progesterone 11α-hydroxylation in a laboratory-scale stirred tank bioreactor. β-Cyclodextrin was used to enhance steroid solubility in aqueous transformation media and consequently to increase the rate of steroid hydroxylation. Batch and continuous processes were performed with pellets of different average diameters, ranging from less than 1 mm to 7.5 mm. Mathematical model simulations of both operational modes confirmed the previously defined Michaelis–Menten kinetics for the biotransformation. A decrease in overall hydroxylation rate was noticed when pellets larger than 5 mm were used, which correlated with the lower area of outer surface of agglomerates where, presumably, most of the enzyme induction had taken place.

Kinetics of catalytic transfer hydrogenation of soybean oil

The catalytic transfer hydrogenation of soybean oil was studied by using various concentrations of sodium formate solutions, an emulsifier and paladium on a carbon catalyst. Sodium formate concentration and addition of the emuldifier significantly affect the reaction rate because of their influence on the liquid/liquid interface. Under conditions in which diffusion effects are eliminated, all reactions carried out in diluted sodium formate solution obey first-order kinetics with respect to fatty acids. This allows control over the hydrogenation process of soybean oil, needed to obtain partially hydrogenated oil containing about 1% linolenic acid and a relatively high level of linoleic acid with no increase in the stearic acid concentration.

Continuous steroid biotransformations in microchannel reactors

The use of microchannel reactor based technologies within the scope of bioprocesses as process intensification and production platforms is gaining momentum. Such trend can be ascribed a particular set of characteristics of microchannel reactors, namely the enhanced mass and heat transfer, combined with easier handling and smaller volumes required, as compared to traditional reactors. In the present work, a continuous production process of 4-cholesten-3-one by the enzymatic oxidation of cholesterol without the formation of any by-product was assessed. The production was carried out within Y-shaped microchannel reactors in an aqueous-organic two-phase system. Substrate was delivered from the organic phase to aqueous phase containing cholesterol oxidase and the product formed partitions back to the organic phase. The aqueous phase was then forced through a plug-flow reactor, containing immobilized catalase. This step aimed at the reduction of hydrogen peroxide formed as a by-product during cholesterol oxidation, to avoid cholesterol oxidase deactivation due to said by-product. This setup was compared with traditional reactors and modes of operation. The results showed that microchannel reactor geometry outperformed traditional stirred tank and plug-flow reactors reaching similar conversion yields at reduced residence time. Coupling the plug-flow reactor containing catalase enabled aqueous phase reuse with maintenance of 30% catalytic activity of cholesterol oxidase while eliminating hydrogen peroxide. A final production of 36 m of cholestenone was reached after 300 hours of operation.

Assessment of physical leaching processes of some elements in soil upon ingestion by continuous leaching and modeling.

The physical processes controlling the desorption of some elements (B, Cd, Co, Mn, Ni, and Sr) from soils in a continuous leaching system representing the human stomach are investigated here by fitting experimental leaching data to a mathematical particle diffusion model. Soil samples (50 mg) from Cornwall, UK, contained in a flow-through extraction chamber (ca. 6.5 mL) were intimately contacted with artificial gastric solution at various flow rates (0.42-1.42 mL min(-1)) for up to ca. 4 h, followed by analysis of the fractions collected with inductively coupled plasma mass spectrometry (ICP-MS). The leaching profiles of the various elements were fitted to a mathematical model incorporating two mass transfer processes (liquid film diffusion and apparent solid phase diffusion) to determine the effective external mass transfer coefficient (beta) and the apparent intraparticle soil diffusion coefficient (D(a)). A system of partial differential equations was solved numerically with a finite difference discretization of the computational domain allowing the rate limiting physical desorption process(es) for each element to be determined. The (thermodynamic) driving force of the leaching process is defined by the distribution coefficient (K(d0)) between soil and leachant. Although the K(d0) values investigated are very similar (ca. 6-15 L kg(-1)) for the elements studied with the exception of B (ca. 2.7 L kg(-1)), the leaching profiles are very different due to diffusion-limited processes. The elements may be classified as limited by beta (B, Sr, and Cd), by D(a) (Co, and Mn) or by beta and D(a) (Ni). This results in quantifiable parameters for the liability of elements in soil upon ingestion which may be implemented in future risk assessment protocols.

Feasibility of Carbon Nanofiber Catalyst Support for the Heterogeneous Fenton Process

AbstractThe heterogeneous Fenton oxidation reaction was investigated at two different catalytic supports including the blank alumina plates and alumina plates with thin carbon nanofiber (CNF) layer. Iron (III) oxide was used as a catalyst and propionic acid (PA) was studied as a model organic compound. A carbon nanofiber layer and a thin catalytic layer of iron (III) oxide were prepared using the chemical vapor deposition method with acetylene and ferrocene precursors. The reaction rate of heterogeneous Fenton oxidation was compared with the rate of homogeneous reaction. Obtained results indicate that the reaction rate is significantly higher at homogeneous Fenton oxidation at high temperature (70°C), however, the reaction rate for homogeneous and heterogeneous oxidation is comparable at room temperature (25°C) if carbon nanofiber support is used for the iron (III) oxide catalyst.