Technology
What is the Dynamic Gastric Model?
The Dynamic Gastric Model (DGM) is a bench-top computer controlled in vitro system that simulates digestion in the human stomach, allowing accurate prediction and understanding of the behaviour of foods or drug preparations within the human gut during digestion in real time. The DGM was developed at the Quadram Institute Bioscience (formerly the Institute of Food Research) and is the first known in vitro model developed to combine emerging scientific knowledge of the physical, mechanical and biochemical environments experienced by the luminal contents of the human stomach, in a single predictive system.
The DGM fully replicates changes in pH, enzyme addition, shearing, mixing and retention time of an adult human stomach. These complex biochemical conditions and array of gastric forces are crucial for the prediction of the bio-behaviour of API’s (Active Pharmaceutical Ingredient’s) and dosage forms for oral delivery (e.g. capsule, tablet, powder and liquid). Samples can be taken at any time during the process and analysed to predict the bio-accessibility of active components such as nutrients and drugs.
As in the human stomach, masticated material is processed in functionally distinct zones. Meals ranging from a glass of water to the FDA high fat American breakfast and other complex multiphase meals are fed into the model. Within the fundus/main body of the DGM, gastric acid (as a function of measured pH) and enzyme secretions (as a function of volume of meal chyme present in the DGM) are introduced dynamically around the outside of the food bolus simulating secretion from the walls of the stomach at physiological rates. The main body is subjected to gentle, rhythmic massaging, replicating the inhomogeneous mixing of the human stomach. Secretion rates adapt dynamically to the changing conditions within this compartment (acidification, fill state). Portions of gastric contents are then moved into the DGM antrum in the same processed form and at the same rate as seen in vivo where they are subjected to physiological shear and grinding forces, to reproduce the breakdown of the food particles and the preferential sieving observed in vivo, before ejection from the machine for further analysis.
Development of the Dynamic Gastric Model
Development of the Dynamic Gastric Model
Development of the Dynamic Gastric Model
The key driver for the development of the Dynamic Gastric Model (DGM) was to provide a physiologically relevant in vitro tool that incorporates the realisation that the structure and combination of foods and pharmaceuticals can significantly affect the rate, site and extent of release and absorption of the active component of a pharmaceutical preparation. The pattern of absorption, particularly the magnitude and duration of plasma pharmaceutical concentration excursion has substantial implications for both the effectiveness of the food or pharmaceutical and for the health of the individual.
In the first stage of developing the Model, Echo Planar Magnetic Resonance Imaging (EPI) (in collaboration with the Sir Peter Mansfield Magnetic Resonance Centre at Nottingham University) was used to make in situ and non-invasive measurements of gastro-intestinal processing of complex meals in human volunteers. From these studies essential data was collected on the digestion of complex meals and the influence of structure, hydration, mixing, shear, transport and delivery within the gastrointestinal tract coupled with measurements of physiological and psychometric changes. The results have given entirely novel insight into the physical processing within the lumen of the human gut and have provided data on the key conditions that control processing. These conditions are being replicated in the DGM.
Development of the Dynamic Gastric Model
Development of the Dynamic Gastric Model
EP-MRI traces show how gastric secretion (red pixels) can take over an hour to penetrate into the core of a light meal (yellow pixels) giving rise to a highly heterogeneous pH/enzymic environment within the gastric compartment. This characteristic gastric secretion disposition is replicated in Dynamic Gastric Model.
Marciani LG et al (2001). Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI. American Journal of Physiology-Gastrointestinal and Liver Physiology, 280(6), G1227–G1233. https://doi.org/10.1152/ajpgi.2001.280.6.g1227
Vardakou and colleagues at the Quadram Institute Bioscience (formerly the Institute of Food Research) assessed the grinding forces of the DGM by comparing the breakdown of agar gel beads with human in vivo data. The DGM was fed high (HV) and low (LV) viscosity meals with agar gel beads of varying fracture strength. As displayed in graph (a), in vivo analysis of the processing of the beads found increased meal viscosity reduced Mean Breaking Time (MBT) of harder beads (Marciani L et al., 2001). Graph (b) displays the results of in vitro analysis using the Dynamic Gastric Model, showing a similar finding. Results from this study suggest the DGM was able to mimic the gastric forces in vivo.
Vardakou M et al. (2011). Achieving antral grinding forces in biorelevant in vitro models: comparing the USP dissolution apparatus II and the dynamic gastric model with human in vivo data. AAPS PharmSciTech; 12(2): 620-626. https://doi.org/10.1208/s12249-011-9616-z
Marciani L et al. (2001). Assessment of antral grinding of a model solid meal with echo-planar imaging. 280(5), G844–G849. https://doi.org/10.1152/ajpgi.2001.280.5.g844
Plant Bioscience Limited, a technology development and intellectual property management company is the owner of the patent rights to the Dynamic Gastric Model, originally created at the Quadram Institute Bioscience (formerly the Institute of Food Research) by the inventors Dr Martin Wickham and Richard Faulks
