Peritoneal drug transport
Wim P. Ceelen, Edward A. Levine in Intraperitoneal Cancer Therapy, 2015
In the perioperative setting, drug delivery can be enhanced considerably. Two or more catheters can be placed in the peritoneal cavity: one or more catheters for drug input and the other catheter(s) for removal of solution. Solutions warmed to temperatures greater than body temperature (approximately 41°C) may be infused rapidly into the peritoneal cavity and withdrawn in the second catheter. This technique will set up higher concentrations if solution is fed from a large reservoir that the loss of drug is relatively small. Heating of the drug causes vasodilation in the surrounding vessels, and there is likely an increase in penetration into both normal tissue and neoplastic tissue [89–93]. Other methods include the surgeon massaging/stirring the treatment solution in situ within the cavity [94]. Either of these techniques may help to solve the problem of residence time. If a greater portion of the peritoneal surface area is covered by the solution and the concentration of the drug is maintained constant, then the area into the curve for the surface contact concentration should be maximized. Randomized controlled trials of these techniques will help in the decision to implement the additional procedures [95].
Virally Induced Water and Divalent Cation Movement Across Plasma Membranes
Gheorghe Benga in Water Transport in Biological Membranes, 1989
There is an alternative explanation which does not invoke a boundary layer that is more conventional in its assumptions, though the unexpectedly slow exchange rate makes it less likely. It is as follows. In a simple two compartment system, altering the proportions of the compartments would change the apparent relaxation times by changing the residence time of the compartment. From Equation 9, the residence time by definition follows the population size provided no other parameters change. According to the relative sizes of the relaxation and residence times of a compartment, the observed relaxation time will change. If the residence time is much shorter than the relaxation time, the observed relaxation will follow the population size. Conversely, if the relaxation time is much shorter than the residence time, the population size will have little effect on the observed relaxation rate. Thus, reducing the proportion of extracellular medium by concentrating the cell suspension, from say 80 to 20%, would, if the residence time were shorter than the relaxation time, reduce the observed relaxation time of that compartment by about fourfold, as is observed (see Table 4).
Medical Internal Dosimetry for High-Dose Radionuclide Therapies
David M. Goldenberg in Cancer Therapy with Radiolabeled Antibodies, 1995
To determine residence time, the percent administered activity over time in each source region is plotted and fitted to a mathematical function or series of functions. The uptake of administered activity by source organs is usually quite rapid and is followed by exponential clearance with a characteristic clearance half-time.
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.
Advantages and limitations of amino acid PET for tracking therapy response in glioma patients
Published in Expert Review of Neurotherapeutics, 2020
Karl-Josef Langen, Alexander Heinzel, Philipp Lohmann, Felix M. Mottaghy, Norbert Galldiks
Therefore, a number of diagnostic approaches with a focus on metabolic and functional imaging methods are under investigation [3]. Positron emission tomography (PET) is a well-established method in nuclear medicine that is able to detect the distribution of radiolabelled molecules in the human body with high sensitivity and a spatial resolution of 3–5 mm. Since numerous metabolic substrates, receptor ligands or pharmaceuticals can be labeled with positron-emitting isotopes such as carbon-11, nitrogen-13 or fluorine-18, PET offers great potential for the assessment of metabolic and physiological processes. However, radiolabelling of the molecules with short-lived positron emitters is a rather sophisticated procedure. In addition, the tracers must meet a number of conditions such as high in vivo stability, high specificity and a sufficient residence time in the target tissue in order to be clinically useful.
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