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Biomedical subjects

N W Kossen

Publications and source records attributed to N W Kossen.

4 recordsLinked to original sources

A particulate pulse-release system and mathematical description with the Maxwell-Stefan theory.

In this contribution both the development of a multi-particulate delayed release system with release properties dependent on the swelling of an UV crosslinked coating and a mathematical model to describe its release properties are presented. The formulation consists of a water-soluble core coated with a copolymer of methacrylic acid and ethyl acrylate. Incorporating a network of crosslinked pentaerythritol triacrylate decreases the water-solubility of the coating. After immersing the formulation in water the coating will take up water and subsequently swell in such a degree that the diffusion coefficient of water in the coating will increase. This makes the coating permeable to the dissolved components present in the core. The swelling kinetics of the coating are such that the formulation has a pulse-release profile, i.e. a fast release of the contents is obtained after a pre-determined lag-time. Both the coating thickness and the duration of the UV crosslinking time can be used to adjust the lag-time. The experimental results are used to estimate the Maxwell-Stefan diffusion coefficients of water in the coating. The relation between the Maxwell-Stefan diffusion coefficient and the mole fraction of water in the coating differs from results found in the literature. However, the prediction of the release time based on the presented model is in good agreement with the experimental findings.

Acrylates↗

Fluid bed agglomeration with a narrow droplet size distribution.

In the fluid bed agglomeration processes liquid distribution influences the agglomerate growth. We developed a new nozzle that produces uniform droplets, which allows droplets to be easily controlled in size independently of liquid- and airflow of the nozzle. It was found that the spray rate and the mixing in the spray zone determine the average granule size and that there is linear relation between the number of droplets of which a granule consists and its volume, at the early stage of the process. The nucleation ratio factor introduced in this paper depends on the material properties of binder liquid and powder particles and is a useful parameter to describe the binder liquid efficiency. The decline of the growth rate of granules during the agglomeration process was due to the less sufficient rewetting of granules resulting in less growth. A linear relation was found between tracer mass added to the binder liquid and the granule mass in an early stage of the process. Solubility of the tracer was found not to influence its distribution. The new nozzle proves to be a good tool to study the effect of wetting and growth of granules.

Algorithms↗

The morphology of filamentous fungi.

The morphology of fungi has received attention from both pure and applied scientists. The subject is complicated, because many genes and physiological mechanisms are involved in the development of a particular morphological type: its morphogenesis. The contribution from pure physiologists is growing steadily as more and more details of the transport processes and the kinetics involved in the morphogenesis become known. A short survey of these results is presented. Various mathematical models have been developed for the morphogenesis as such, but also for the direct relation between morphology and productivity--as production takes place only in a specific morphological type. The physiological basis for a number of these models varies from thorough to rather questionable. In some models, assumptions have been made that are in conflict with existing physiological know-how. Whether or not this is a problem depends on the purpose of the model and on its use for extrapolation. Parameter evaluation is another aspect that comes into play here. The genetics behind morphogenesis is not yet very well developed, but needs to be given full attention because present models and practices are based almost entirely on the influence of environmental factors on morphology. This makes morphogenesis rather difficult to control, because environmental factors vary considerably during production as well as on scale. Genetically controlled morphogenesis might solve this problem. Apart from a direct relation between morphology and productivity, there is an indirect relation between them, via the influence of morphology on transport phenomena in the bioreactor. The best way to study this relation is with viscosity as a separate contributing factor.

Biological Transport↗

Microdialysis of glucose in subcutaneous adipose tissue up to 3 weeks in healthy volunteers.

OBJECTIVE: To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue. RESEARCH DESIGN AND METHODS: Glucose concentrations in the subcutaneous adipose tissue of five healthy subjects (age 25 +/- 2.7 years, BMI 23.2 +/- 2.3 kg/m2 [mean +/- SD]) were measured by the microdialysis technique and compared with blood glucose. We applied microdialysis probes with hollow fibers of various membrane length (10-35 mm), used eight perfusion flow rates (0.5-20 microl/min), and perfused four glucose solutions (0.0, 2.8, 8.3, 11.1 mmol/l). RESULTS: After implantation, a substantial decrease in glucose recovery to the lowest value of 26 +/- 10% of the final plateau value was noted during the first few hours (n = 4). Recovery increased and stabilized after 5-9 days at 84.0 +/- 7.4% of capillary blood glucose when a flow rate of 0.5 microl/min was applied. According to the zero net-flux method, the glucose concentration in equilibrium, Cequi, with the surrounding tissue can be obtained. This concentration also decreases; however, 1 h after recovery, Cequi increases again over 1 or 2 days to a stable value that is not significantly different from the measured capillary blood glucose (P < 0.05). Using various perfusion flow rates and probes (membrane length 10-35 mm), it is shown that diffusion is the rate-limiting process for glucose transport through tissue. CONCLUSIONS: Insertion of the microdialysis probes causes damage to the adipose cells and the vascular bed around the probe. Glucose recovery decreases because of a lower blood supply. In 5-9 days, glucose recovery increases; apparently, this time is needed to repair the microstructure of tissue around the probe. After stabilization of the recovery, no loss of probe permeability, which is due to biocompatibility problems, was seen. The change during the 2 days in equilibrium concentration is probably caused by an inflammation reaction that consumes glucose around the probe. The individual increase in recovery during the 1st days after probe insertion until a stable plateau value is reached (flow rate >0 microl/min) is complicated for short-term clinical glucose measurements in adipose tissue. After stabilization, the mean equilibrium concentration of all subjects was equal to the mean capillary blood glucose concentration. Therefore, we conclude that capillary blood glucose concentration probably is the driving force for diffusion through the capillary wall into the probe and is not some interstitial concentration.

Adipose Tissue↗