Research Center Pharmaceutical Engineering

Graz, Austria

Research Center Pharmaceutical Engineering

Graz, Austria

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Planchette C.,University of Marne-la-Vallée | Planchette C.,Research Center Pharmaceutical Engineering | Biance A.-L.,University Claude Bernard Lyon 1 | Pitois O.,University Paris Est Creteil | Lorenceau E.,University Paris Est Creteil
Physics of Fluids | Year: 2013

Armored interfaces refer to fluid interfaces on which a compact monolayer of particles is adsorbed. In this paper, we probe their robustness under impact. For such an investigation, the impact of a drop (covered or not by particles) on a flat armored interface is considered. Two regimes are observed: small drops impacting at low velocities do not coalesce, while bigger drops falling at higher velocities lead to coalescence. The coalescence which occurs when the impacting drop has just reached its maximum extension directly results from the formation of bare regions within the armor. We therefore propose a geometric criterion to describe this transition. This simple modeling is able to capture the dependence of the measured velocity threshold with particle size and drop diameter. The additional robustness experienced by double armors (both drop and puddle covered) results in an increase of the measured velocity threshold, which is quantitatively predicted. © 2013 AIP Publishing LLC.

Planchette C.,University Paris Est Creteil | Planchette C.,Research Center Pharmaceutical Engineering | Lorenceau E.,University Paris Est Creteil | Biance A.-L.,University Claude Bernard Lyon 1
Soft Matter | Year: 2012

The mechanical properties of particle laden interfaces are investigated by studying capillary wave propagation along the interface. Interfaces are coated with monodisperse silica hydrophobic particles with diameters ranging from 35 μm to 159 μm. The surfaces are prepared with a particle density just above that required for random close packing, so that no macroscopic wrinkles can be observed. Measurements of wave celerity versus wavelength and a comparison of the results with theory allow us to define the stretching modulus and the bending stiffness of such an interface. These quantities are for the first time measured independently and under a large range of frequencies (100 Hz-900 Hz). Particle diameters and contact angles have been varied systematically. We observe that the stretching modulus does not depend on the particle size, while the bending stiffness exhibits variations with the square of particle diameter. These results are confronted with previous results on quasistatic assays and with theoretical predictions on the capillary origin of bending stiffness, showing a good agreement. Similarities and differences are discussed. © 2012 The Royal Society of Chemistry.

Bolivar J.M.,University of Graz | Wiesbauer J.,University of Graz | Wiesbauer J.,Research Center Pharmaceutical Engineering | Nidetzky B.,University of Graz | And 2 more authors.
Trends in Biotechnology | Year: 2011

The state of the art in the application of microstructured flow reactors for biocatalytic process research is reviewed. A microstructured reactor that is fully automated and analytically equipped presents a powerful screening tool with which to perform biocatalyst selection and optimization of process conditions at intermediary stages of process development. Enhanced mass transfer provided by the microstructured reactor can be exploited for process intensification, particularly during multiphase biocatalytic processing where mass transfer across phase boundaries is often limiting. Reversible immobilization of enzymes in microchannels remains a challenge for flexible realization of biotransformations in microstructured reactors. Compartmentalization in microstructured reactors could be useful in performing multistep chemoenzymatic conversions. © 2011 Elsevier Ltd.

Neugebauer P.,University of Graz | Khinast J.G.,University of Graz | Khinast J.G.,Research Center Pharmaceutical Engineering
Crystal Growth and Design | Year: 2015

Protein crystals have many important applications in many fields, including pharmaceutics. Being more stable than other formulations, and having a high degree of purity and bioavailability, they are especially promising in the area of drug delivery. In this contribution, the development of a continuously operated tubular crystallizer for the production of protein crystals has been described. Using the model enzyme lysozyme, we successfully generated product particles ranging between 15 and 40 μm in size. At the reactor inlet, a protein solution was mixed with a crystallization agent solution to create high supersaturations required for nucleation. Along the tube, supersaturation was controlled using water baths that divided the crystallizer into a nucleation zone and a growth zone. Low flow rates minimized the effect of shear forces that may impede crystal growth. Simultaneously, a slug flow was implemented to ensure crystal transport through the reactor and to reduce the residence time distribution. © 2015 American Chemical Society.

Lorantfy B.,Vienna University of Technology | Lorantfy B.,Research Center Pharmaceutical Engineering | Seyer B.,Vienna University of Technology | Herwig C.,Vienna University of Technology
New Biotechnology | Year: 2014

Extreme halophilic Archaea are extremophile species which can thrive in hypersaline environments of up to 3-5. M sodium chloride concentration. Although their ecology and physiology are widely identified on the microbiological level, little emphasis has been laid on quantitative bioprocess development with extreme halophiles.The goal of this study was to establish, on the one hand, a methodological basis for quantitative bioprocess analysis of extreme halophilic Archaea with an extreme halophilic strain as an example. Firstly, as a novel usage, a corrosion resistant bioreactor setup for extreme halophiles has been implemented. Then, paying special attention to total bioprocess quantification approaches, an indirect method for biomass quantification using on-line process signals was introduced. Subsequently, robust quantitative data evaluation methods for halophiles could be developed, providing defined and controlled cultivation conditions in the bioreactor and therefore obtaining suitable quality of on-line as well as off-line datasets.On the other hand, new physiological results of extreme halophiles in bioreactor have also been obtained based on the quantitative methodological tools. For the first time, quantitative data on stoichiometry and kinetics were collected and evaluated on different carbon sources. The results on various substrates were interpreted, with proposed metabolic mechanisms, by linking to the reported primary carbon metabolism of extreme halophilic Archaea. Moreover, results of chemostat cultures demonstrated that extreme halophilic organisms show Monod-kinetics on different sole carbon sources. A diauxic growth pattern was described on a mixture of substrates in batch cultivations.In addition, the methodologies presented here enable one to characterize the utilized strain Haloferax mediterranei (HFX) as a potential new host organism. Thus, this study offers a strong methodological basis as well as a fundamental physiological assessment for bioreactor quantification of extreme halophiles that can serve as primary knowledge for applications of extreme halophiles in biotechnology. © 2013 Elsevier B.V.

Mohr S.,University of Graz | Mohr S.,Research Center Pharmaceutical Engineering | Pilaj S.,University of Graz | Schmid M.G.,University of Graz
Electrophoresis | Year: 2012

In recent years, cathinone derivatives have entered the global drug market and caused serious social problems in many European countries. Modification of the basic structure of cathinone leads to a multitude of derivatives, including the most popular representative mephedrone. All those substances contain a stereogenic center and therefore two isoforms exist. As it is the case with many chiral active pharmaceutical ingredients, even the pharmacological effect of the enantiomers of those psychoactive compounds may differ. During this research, an easy-to-prepare chiral capillary zone electrophoresis method for the enantioseparation of a set of 19 cathinone derivatives was developed. Testing different types of cyclodextrin (CD), including native-β-CD, carboxymethyl-β-CD, 2-hydroxypropyl-β-CD, sulfated-β-CD, and native γ-CD, best results were obtained with the negatively charged sulfated-β-CD. The effect of the CD concentration, the temperature, and the addition of ACN to the BGE on the enantioseparation is shown by three model compounds. Under optimal conditions, using 20 mg/mL sulfated-β-CD in 50 mM ammonium acetate buffer pH = 4.5 containing 10% v/v ACN at a cassette temperature of 40°C and with an applied voltage of 20 kV, all derivatives except methedrone were resolved in their enantiomers within 20 min. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Teubl B.J.,University of Graz | Absenger M.,Medical University of Graz | Frohlich E.,Medical University of Graz | Leitinger G.,Medical University of Graz | And 3 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

An important area for future research lies in finding a drug delivery system across or into the oral mucosa. However, to design such systems, simplified biological models are necessary so that the mechanisms and/or interactions of interest can readily be studied. The oral epithelium is covered by a complex mucus layer, which enables exchange of nutrients and provides lubrication. However, it has been demonstrated that mucus has an impact on the mobility of nanoparticles and drug molecules. Thus, we aimed to develop an advanced buccal in vitro model for studying transport of nanoparticles, taking the mucus layer into account. First, animal mucins (porcine gastric, bovine submaxillary) were compared with natural human mucin regarding chemical and morphological structure. Second, an "external" mucus layer was prepared by a film method and deposited onto an oral cell line (TR 146), cultured on transwells®. Adherence of the mucin fibers was evaluated and the viability of the model was assessed. Nanoparticle transport studies were performed with this advanced in vitro model and an ex vivo diffusion system. The results revealed that porcine mucin is most similar to human natural mucin in chemical structure and morphology. Both the bovine and porcine mucin fibers adhered onto the oral cells: Due to the different morphology of bovine mucin, the viability of the oral cells decreased, whereas porcine mucin maintained the viability of the model for more than 48 h. Comparison of in vitro data with ex vivo data suggested reliability of the advanced buccal in vitro model. Additionally, it was demonstrated that the mucus layer in the oral cavity also acts as a strong barrier for the mobility of nanoparticles. © 2013 Elsevier B.V. All rights reserved.

Wiesbauer J.,Research Center Pharmaceutical Engineering | Wiesbauer J.,University of Graz | Prassl R.,Medical University of Graz | Nidetzky B.,Research Center Pharmaceutical Engineering | Nidetzky B.,University of Graz
Langmuir | Year: 2013

Soluble proteins are often highly unstable under mixing conditions that involve dynamic contacting between the main liquid phase and a gas phase. The recombinant human growth hormone (rhGH) was recently shown to undergo aggregation into micrometer-sized solid particles composed of non-native (mis- or unfolded) protein, once its solutions were stirred or shaken to generate a continuously renewed air-water interface. To gain deepened understanding and improved quantification of the air-water interface effect on rhGH stability, we analyzed the protein's aggregation rate (ragg) at controlled specific air-water surface areas (aG/L) established by stirring or bubble aeration. We show that in spite of comparable time-averaged values for a G/L (≈ 100 m2/m3), aeration gave a 40-fold higher ragg than stirring. The enhanced ragg under aeration was ascribed to faster macroscopic regeneration of free aG/L during aeration as compared to stirring. We also show that ragg was independent of the rhGH concentration in the range 0.67 - 6.7 mg/mL, and that it increased linearly dependent on the available aG/L. The nonionic surfactant Pluronic F-68, added in 1.6-fold molar excess over rhGH present, resulted in complete suppression of ragg. Foam formation was not a factor influencing ragg. Using analysis by circular dichroism spectroscopy and small-angle X-ray scattering, we show that in the presence of Pluronic F-68 under both stirring and aeration, the soluble protein retained its original fold, featuring native-like relative composition of secondary structural elements. We further provide evidence that the efficacy of Pluronic F-68 resulted from direct, probably hydrophobic protein-surfactant interactions that prevented rhGH from becoming attached to the air-water interface. Surface-induced aggregation of rhGH is suggested to involve desorption of non-native protein from the air-water interface as the key limiting step. Proteins or protein aggregates released back into the bulk liquid appear to be essentially insoluble. © 2013 American Chemical Society.

Mohr S.,University of Graz | Mohr S.,Research Center Pharmaceutical Engineering | Taschwer M.,University of Graz | Schmid M.G.,University of Graz
Chirality | Year: 2012

Cathinone derivatives gained high popularity on the recreational drugs market during the past 10 years. All these compounds are chiral, and the pharmacological potency of the enantiomers of these stimulants is supposed to differ. The goal of this research was to develop a reliable and easy-to-perform high-performance liquid chromatography ultraviolet method for the chiral separation of a set of 24 cathinone derivatives. A commercially available CHIRALPAK® AS-H column consisting of amylose tris [(S)-α- methylbenzylcarbamate] coated on 5-μm silica gel was found to be suitable to resolve a majority of the tested compounds. High-performance liquid chromatography measurements were performed in normal phase mode under isocratic conditions with a mobile phase consisting of hexane, isopropanol, and triethylamine at a flowrate of 1 ml/min. The ratio between hexane and isopropanol was optimized by means of three model substances. Under final conditions with a mobile phase of hexane, isopropanol, and triethylamine (97:3:0.1), 19 out of 24 compounds were successfully resolved into their enantiomers and detected at a wavelength of 254 nm. A correlation between the substituents of the nitrogen atom and the separation results are shown. Furthermore, enantiomer separation results of four cathinone derivatives were compared with the results of their amphetamine analogs. Copyright © 2012 Wiley Periodicals, Inc.

Sungkorn R.,University of Graz | Derksen J.J.,University of Alberta | Khinast J.G.,Research Center Pharmaceutical Engineering
AIChE Journal | Year: 2012

Simulations of a gas-liquid stirred reactor including bubble breakage and coalescence were performed. The filtered conservation equations for the liquid phase were discretized using a lattice-Boltzmann scheme. A Lagrangian approach with a bubble parcel concept was used for the dispersed gas phase. Bubble breakage and coalescence were modeled as stochastic events. Additional assumptions for bubble breakup modeling in an Euler-Lagrange framework were proposed. The action of the reactor components on the liquid flow field was described using an immersed boundary condition. The predicted number-based mean diameter and long-term averaged liquid velocity components agree qualitatively and quantitatively well with experimental data for a laboratory-scale gas-liquid stirred reactor with dilute dispersion. Effects of the presence of bubbles, as well as the increase in the gas flow rate, on the hydrodynamics were numerically studied. The modeling technique offers an alternative engineering tool to gain detailed insights into complex industrial-scale gas-liquid stirred reactors. © 2011 American Institute of Chemical Engineers (AIChE).

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