Ralph Lietzow

Stabilized nanoparticles of phytosterol by rapid expansion from supercritical solution into aqueous solution.

The basic objective of this work was to form stable suspensions of submicron particles of phytosterol, a water-insoluble drug, by rapid expansion of supercritical solution into aqueous solution (RESSAS). A supercritical phytosterol/CO2 mixture was expanded into an aqueous surfactant solution. In these experiments 4 different surfactants were used to impede growth and agglomeration of the submicron particles resulting from collisions in the free jet. The concentration of the drug in the aqueous surfactant solution was determined by high-performance liquid chromatography, while the size of the stabilized particles was measured by dynamic light scattering. Submicron phytosterol particles (<500 nm) were stabilized and in most cases a bimodal particle size distribution was obtained. Depending on surfactant and concentration of the surfactant solution, suspensions with drug concentrations up to 17 g/dm3 could be achieved, which is 2 orders of magnitude higher than the equilibrium solubility of phytosterol. Long-term stability studies indicate modest particle growth over 12 months. Thus, the results demonstrate that RESSAS can be a promising process for stabilizing submicron particles in aqueous solutions.

Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling

An increasing number of newly developed pharmaceutical substances are poorly soluble in both aqueous and organic media. Thus, the application of oral or injectable drugs is often limited by its low bioavailability. An alternative and promising method to improve the bioavailability of pharmaceutical agents is the production of nanoscale particles by the rapid expansion of supercritical solutions (RESS). Our research is aimed towards an improved understanding of the underlying physical phenomena of the relationship between the process conditions and the particle characteristics. Therefore, experimental investigations and numerical simulations were performed. RESS experiments with the pharmaceutical substances β-sitosterol, griseofulvin, and ibuprofen led to particle sizes in the range of 240±80 nm. In addition, as one step towards intravenous application of poorly soluble drugs, β-sitosterol was used to produce aqueous suspensions of a water-insoluble drug with a particle size smaller than or equal to those produced by RESS into air. RESS modeling is focused on the flow through the nozzle, the supersonic free jet, the mach shock, and particle growth in the expansion unit. The comparison with experimental results shows a good agreement in the general trends but does not match exactly the measured mean particle sizes.

High Temperature Superconductor Current Leads for WENDELSTEIN 7-X and JT-60SA

Forschungszentrum Karlsruhe has taken over the responsibility for the design, construction and testing of the High Temperature Superconductor (HTS) current leads for two fusion experiments, i.e. the stellarator WENDELSTEIN 7-X (W7-X) and the satellite tokamak JT-60SA. W7-X is presently under construction at the Greifswald branch of the Max-Planck-Institute for Plasma Physics and consists of 50 non-planar and 20 planar coils with a maximum conductor current of 17.6 kA. In total 14 current leads are required with a nominal current of 14 kA that are mounted upside down with the warm end at the bottom. In the frame of the Broader Approach Agreement between Japan and the EU and concomitantly to the ITER project, the satellite tokamak project JT-60SA has been agreed in 2006. The magnet system of JT-60SA consists of 18 toroidal field coils, 4 central solenoid modules and 7 poloidal field coils. In total 26 leads mounted in vertical, normal position are required. For W7-X and JT-60SA a common basic design will be used which will be adapted to the special needs of the machines. All current leads will be of the Cu-HTS binary type. The HTS part covers the range between 4.5 K and 60 K and is cooled by heat conduction from the 4.5 K end, only. The Cu heat exchanger is cooled with 50 K He and covers the range between 60 K and room temperature. The paper describes the status of the HTS current lead development for W7-X and JT-60SA.

Test Results of the High Temperature Superconductor Prototype Current Leads for Wendelstein 7-X

The Karlsruhe Institute of Technology (which is a merger of former Forschungszentrum Karlsruhe and Karlsruhe University) is responsible for the design, construction and testing of the high temperature superconductor (HTS) current leads for the stellarator Wendelstein 7-X (W7-X) which is presently under construction at the Greifswald branch of the Max-Planck-Institute for Plasma Physics. The current leads are of the binary type, the HTS part covering the temperature range between 4.5 K and 60 K while the heat exchanger covers the range between 60 K and room temperature being cooled by 50 K He. In total 2 prototypes and 14 series current leads are required with a nominal current of 14 kA and a maximum current of 18.2 kA. The paper describes the design and first test results of the prototype HTS current leads.

Test Arrangement for the W7-X HTS-Current Lead Prototype Testing

The Karlsruhe Institute of Technology (KIT) is responsible for the design, construction and testing of the high temperature superconductor (HTS) current leads for the stellarator Wendelstein 7-X (W7-X) which is presently under construction at the Greifswald branch of the Max-Planck-Institute for Plasma Physics. Because the W7-X current leads are mounted with the warm end at the bottom a special test cryostat has been built and is attached to the main cryostat of the TOSKA facility of KIT. Two prototypes of these current leads are tested in this cryostat under W7-X relevant conditions. The test conditions with respect to cryogenic, control, current supply, data acquisition and quench detection of the test setup for the prototype test at TOSKA is described. The performance of the MC plug used to power the HTS current leads is described in detail.

Investigation of HTS Current Leads Under Pulsed Operation for JT-60SA

The test of two Wendelstein 7-X (W7-X) prototype high temperature superconductor (HTS) current leads (CL) was extended to dynamic operation, in order to evaluate AC losses in parts of the CL. Trapezoidal and triangular current cycles up to a maximum current of 20 kA with different ramp rates between 0.5 kA/s and 10 kA/s were performed. Temperature changes at the warm end of the HTS-module and the influence on the heat load at the cold end of the CL were studied. Additionally, a DC operation that generates a power loss equivalent to the triangular pulsing run was investigated. AC losses in the low temperature part of the CL are estimated by simplified models and compared to the experimental results of the heat load measurements. The effect of the AC losses on the CL performance is discussed.

Chapter 3.3 – Formation of nanoscale drugs by Rapid Expansion of Supercritical Solutions (RESS): – Experimental and theoretical investigations –

This chapter elaborates experimental and theoretical investigations of the formation of nanoscale drugs by rapid expansion of supercritical solutions (RESS). The particle size of the pharmaceutical substances (3-sitosterol, griseofulvin, and ibuprofen precipitated by RESS was in the range of 160 to 320 nm. The improvement of the bioavailability of the RESS-produced griseofulvin has been verified by dissolution experiments according to the Strieker model. As a first step toward intravenous application of poorly soluble drugs, stable suspensions of nanoscale particles of β-sitosterol were produced. In these experiments, the supercritical mixture was sprayed directly into an aqueous surfactant solution. The particle sizes of β-sitosterol in the aqueous solution were smaller or equal to those produced by RESS into air. These experiments show that the RESS technique is a promising method for the formulation of water-insoluble drugs. The modeling results show that particle growth is not completed in the supersonic free jet, and the post-expansion conditions are an important factor to control particles size. The comparison between experimental and calculated particle size shows a good agreement in the general trends, but does not match exactly the measured mean particle sizes.

A Mathematical Model for the Characterization of Superconducting Level Sensors

An automated level control in cryogenic systems requires a precise and continuous level measurement. If properly characterized, superconducting level sensors are a viable option for the same. The operation of a superconducting level sensor is based on the difference in the heat transfer from the sensor wire to the liquid and the gaseous phases of the cryogen. The higher heat transfer in the liquid phase results in a superconductive status, whereas the lower heat transfer in the gaseous phase results in a normal conductive status with a voltage drop corresponding to the length of the wire in the gaseous phase. Hence, it demands a judicious selection of the sensor and the operational parameters such as the current input, for an accurate level measurement as well as the reduction of the liquid boil off. In this paper, to simulate the operation of a superconducting level sensor, a model has been developed by taking the steady-state heat balance along the sensor wire. It is then used for the investigation of the sensor current, voltage output at various liquid levels, and temperature profile of the sensor wires of NbTi and MgB2 /SS level sensors in LHe. Furthermore, design guidelines have been proposed for an MgB2/SS superconducting level sensor for LH2 level measurement. The parameters considered for the analysis are the sensor wire diameter and the active length. In addition, the effect of an external resistor on the sensor operation is also studied.

Cryogenic experiences during W7-X HTS-current lead tests

The Karlsruhe Institute of Technology (KIT) was responsible for design, production and test of the High Temperature Superconductor (HTS) current leads (CL) for the stellerator Wendelstein 7-X (W7-X). 16 current leads were delivered. Detailed prototype tests as well as the final acceptance tests were performed at KIT, using a dedicated test cryostat assembled beside and connected to the main vacuum vessel of the TOSKA facility. A unique feature is the upside down orientation of the current leads due to the location of the power supplies in the basement of the experimental area of W7-X. The HTS-CL consists of three main parts: the cold end for the connection to the bus bar at 4.5 K, the HTS part operating in the temperature range from 4.5 K to 65 K and a copper heat exchanger (HEX) in the temperature range from 65 K to room temperature, which is cooled with 50 K helium. Therefore in TOSKA it is possible to cool test specimens simultaneously with helium at two different temperature levels. The current lead t...