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Kinetics of Blood to Cell Uptake of Radiotracers*
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
James B. Bassingthwaighte, Bernd Winkle
The cumulative residence time distribution H(t) is the fraction of indicator collected by time t at the output and is the integral of h(t):
Modeling and simulation of continuous powder blending applied to a continuous direct compression process
Published in Pharmaceutical Development and Technology, 2018
Shaun C. Galbraith, Huolong Liu, Bumjoon Cha, Seo-Young Park, Zhuangrong Huang, Seongkyu Yoon
A modeling methodology involving axial and radial tanks-in-series is developed to model the residence time distribution and blend uniformity of a continuous powder blending process. This methodology is then tested against process data coming from a commercial-scale continuous direct compression process manufacturing tablets with a six component formulation. The residence time distribution is measured experimentally by a number of impulse response tests. The one-dimensional TIS flowsheet models were able to successfully describe the experimental measurements within their observed variation when parameter estimation is employed to determine the number of tanks. Back flow was seen to improve the fit of the tail of the distribution but at cost of the peak, further optimization work involving the number of tanks, lag time and split fractions should allow for overall better fits. A two-dimensional TIS model was introduced to produce blend uniformity, represented by RSD, as a model output. The model was able to describe the experimentally observed RSD in the final axial section of the blender indicating this approach can be used to make predictions about blend uniformity. The ability of this approach to yield RTD and RSD outputs is promising and will be developed further by investigating more experimental conditions and looking for relationships between the model parameters (number of tanks and split fractions), operating parameters (throughput and impellor speed) and design parameters (blade configuration).
Automation of a dosing-disc capsule filler from the perspective of reliability and safety
Published in Drug Development and Industrial Pharmacy, 2018
Bernhard Wagner, Thomas Brinz, Stephanie Otterbach, Johannes Khinast
Another scenario, where control of the bed height at a low level may be relevant, is the transition of manufacturing from batch to continuous manufacturing. Here, another parameter, that is, the so called residence time distribution (RTD), becomes important, with a narrow RTD being better than a broad one. The RTD is the basis for addressing issues such as the traceability of materials and the effect of out-of-spec events in manufacturing processes [23]. The residence time of the filling process is influenced by the amount of powder located on the dosing disc. The more powder, the higher the residence time is, as the powder is constantly mixed by the scraper in the bowl. As the amount of powder on the dosing disc is dependent on the powder bed height, the height influences the RTD. A reduction of powder bed height might be an option to reduce the residence time of the process and a PID control can help to facilitate this objective.
Development of a continuous reactor for emulsion-based microencapsulation of hexyl acetate with a polyuria shell
Published in Journal of Microencapsulation, 2019
Sven R. L. Gobert, Marleen Segers, Stijn Luca, Roberto F. A. Teixeira, Simon Kuhn, Leen Braeken, Leen C. J. Thomassen
The flow behaviour inside the residence time reactor is characterised through the residence time distribution (RTD). When a fluid element enters a reactor, its time spent inside the reactor depends on the path it follows. Because different elements follow different paths, there will be a spread on the residence time. This distribution of residence time is a measure of macromixing and is determined through an input-response experiment. The step-input of the reactor is a feed change from a 0.01 M KCl solution (Merk, Darmstadt, Germany), to ultrapure water at 22.2 ml/min. The conductivity of the exit stream is monitored at 1 s intervals with a micro flow cell 829-CE, Model 3082-S-CE digital conductivity metre (Amber Science Inc., Oregon, USA). The resulting conductivity signal in function of time is converted to the F(t) curve, from which the mean residence time, tres, and variance, σ2, are calculated. The RTD is also measured with the emulsion matrix. For this experiment the step input is a switch between a premade emulsion with arabic gum containing 0.1 M KCl, and an in situ generated emulsion with standard arabic gum solution. The TAP is omitted in these formulations to avoid the polymerisation reaction. The experimental distributions are compared to the normalised dispersion model (Equation (8)). Ideal plug flow shows a distribution with zero spread. Flow behaviour that shows minor deviations from ideal plug flow is characterised by a symmetric bell shaped curve which can be fitted by the dispersion model, whereby Dax/uL, the dispersion number, is smaller than 0.01 (Levenspiel 1999).