53 research outputs found
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Overview of mathematical approaches used to model bacterial chemotaxis I: the single cell
Mathematical modeling of bacterial chemotaxis systems has been influential and insightful in helping to understand experimental observations. We provide here a comprehensive overview of the range of mathematical approaches used for modeling, within a single bacterium, chemotactic processes caused by changes to external gradients in its environment. Specific areas of the bacterial system which have been studied and modeled are discussed in detail, including the modeling of adaptation in response to attractant gradients, the intracellular phosphorylation cascade, membrane receptor clustering, and spatial modeling of intracellular protein signal transduction. The importance of producing robust models that address adaptation, gain, and sensitivity are also discussed. This review highlights that while mathematical modeling has aided in understanding bacterial chemotaxis on the individual cell scale and guiding experimental design, no single model succeeds in robustly describing all of the basic elements of the cell. We conclude by discussing the importance of this and the future of modeling in this area
A Model-Based Methodology for Spray-Drying Process Development
Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales
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