Article

Assessing drug release and dissolution in the stomach by means of the Dynamic Gastric Model (DGM): a biorelevant approach

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  • Evotec, Italy
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... The physical forces within the DGM differ with the fundus/main body being subjected to rhythmic squeezing (0.05 Hz) and the antral part higher shear forces. The DGM has been shown to have value in pharmaceutical research predominantly to understand the performance of dosage forms (eg [157][158][159]) rather than ingestible devices. Studies have been conducted to better understand the survival of probiotics in the stomach [160] and to compare the performance of capsule shell materials [159]. ...
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Orally ingestible medical devices offer significant opportunity in the diagnosis and treatment of gastrointestinal conditions. Their development necessitates the use of models that simulate the gastrointestinal environment on both a macro and micro scale. An evolution in scientific technology has enabled a wide range of in vitro, ex vivo and in vivo models to be developed that replicate the gastrointestinal tract. This review describes the landscape of the existing range of in vitro tools that are available to characterize ingestible devices. Models are presented with details on their benefits and limitations with regards to the evaluation of ingestible devices and examples of their use in the evaluation of such devices is presented where available. The multitude of models available provides a suite of tools that can be used in the evaluation of ingestible devices that should be selected on the functionality of the device and the mechanism of its function.
... Past studies in the DGM have involved a wide variety of dosage forms (capsule, tablet, powder, liquid) and types e.g. immediate release, modifi ed release, gastroretentive, self-emulsifying drug delivery system (Vardakou et al. 2011b ;Mercuri et al. 2009Mercuri et al. , 2011. Particularly in the case of gastro-retentives, the ability to introduce sequential meal cycles (e.g. ...
Article
The Dynamic Gastric Model (DGM) was developed at the Institute of Food Research (Norwich, UK) to address the need for an in vitro model which could simulate both the biochemical and mechanical aspects of gastric digestion in a realistic time-dependent manner. As in the human stomach, masticated material is processed in functionally distinct zones: Within the fundus/main body of the DGM, gastric acid and enzyme secretions are introduced around the outside of the food bolus which is subjected to gentle, rhythmic massaging. 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 where they are subjected to physiological shear and grinding forces before ejection from the machine (and subsequent separate duodenal processing). The DGM has been used extensively for both food and pharmaceutical applications, to study, for example, release and bioaccessiblity of nutrients and drugs. The system allows the use of complex food matrices (as used in in vivo studies) and processes these under physiological conditions in real-time, thereby providing a realistic tool for the simulation of human gastric digestion.
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Background: Food digestion rate and location within the gastrointestinal (GI) tract are important for human health. Ideally, food digestion studies should be performed in vivo but this is not always technically, ethically and financially possible. Thus, various in vitro digestion systems have been developed, from static mono-compart- mental to dynamic multi-compartmental models, to simulate food digestive behaviors within the GI tract. Scope and approach: In this review, food digestion process along the GI tract is briefly described. The current in vitro digestion systems with regards to the human GI physiology, and their advantages versus limitations in the understanding of various food digestion processes in the upper GI tract are critically discussed. There is an emphasis on the “near real” dynamic rat (DRSD) and human (DHSI) gastric-intestinal systems, which not only mimic the peristaltic movements and biochemical conditions found in vivo, but also incorporate the gastric morphology and anatomical structures. Key findings and conclusions: Although some in vitro digestion systems reported in literature can be statistically correlated with certain perspectives of food digestion processes in vivo, many physiological, anatomical and geometrical factors that play important roles in determining the digestion rate and extent have been overlooked. The DRSD and DHSI are advantageous in terms of being able to resemble the gastric morphology and anatomy in the rats and humans, respectively. It is of importance that the upper GI anatomy and morphology along with the related biochemical environments and peristaltic movements occurring in vivo should be considered in the de- velopment of more advanced and biologically relevant in vitro digestion systems.
Chapter
The complexity of the local environment of the gastrointestinal tract presents a significant challenge for achieving reliable performance of hydrophilic matrix oral dosages, and designing robustness into the formulation is key to achieving reproducible behaviour in vivo. This chapter outlines the physiological variables which must be taken into account during the development phase, and describes the different in vitro approaches used in attempts to simulate the interactions that may occur between hydrophilic matrix dosage forms and the GI environment in vivo. A series of in vivo case studies describes methods for assessing the clinical performance of hydrophilic matrix dosages using imaging techniques, and gives examples where such tools have been used to elucidate dosage form–food interactions and dosage form gastrointestinal tract interactions. Key findings are summarised from these in vivo case studies, ranging from identification of food effects to assessment of matrix robustness.
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There is an increasing need to understand how food formulations behave in vivo from both food and pharma industries. A number of models have been proposed for the stomach, but few are available for the other parts of the gastrointestinal tract. An experimental rig that simulates the segmentation motion occurring in the small intestine has been developed. The objective of developing such an experimental apparatus was to study mass transport phenomena occurring in the lumen and their potential effect on the concentration of species available for absorption. When segmentation motion was applied the mass transfer coefficient in the lumen side was increased up to a factor of 7. The viscosity of the lumen, as influenced by guar gum concentration, had a profound effect on the mass transfer coefficient. The experimental model was also used to demonstrate that glucose available for absorption, resulting from starch hydrolysis, can be significantly reduced by altering the lumen viscosity. Results suggest that absorption of nutrients could be controlled by mass transfer. Practical Application: To address health-related diseases such as obesity, novel foods that provide advanced functions are required. To achieve the full potential offered by the latest developments in the field of food material science, a fundamental understanding of the behavior of food structures in vivo is required. Using the developed gut model we have demonstrated that absorption of nutrients can be controlled by mass transfer limitations.
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The objective of this study was a comparative investigation of the influence of concomitant food intake on the bioavailability of two nifedipine-containing controlled-release formulations. Adalat OROS and CORAL were compared in a randomised, non-blind, four-way crossover design in 24 healthy, male subjects after single dose administration following a high fat American breakfast or an overnight fast of 12 h, respectively. Plasma samples were withdrawn until 48 h post-dose. In the fasted state, the bioavailability (AUC and C(max) values) was lower for CORAL than for Adalat OROS. Under fed conditions, differences in bioavailability between both products were markedly increased. With respect to the therapeutic use of both products, the most important finding was the significant dose-dumping effect observed after fed administration of CORAL, resulting in nifedipine plasma concentrations of nearly three- to four-fold in 11 of 24 volunteers. The mean ratio of C(max) was 235% comparing CORAL with Adalat OROS under these conditions. The formulation-dependent food interaction observed in this study may be therapeutically relevant, especially in the case of changing administration conditions or switching from one product to the other.
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Solubilities measured in water are not always indicative of solubilities in the gastrointestinal tract. The use of aqueous solubility to predict oral drug absorption can therefore lead to very pronounced underestimates of the oral bioavailability, particularly for drugs which are poorly soluble and lipophilic. Mechanisms responsible for enhancing the luminal solubility of such drugs are discussed. Various methods for estimating intra-lumenal solubilities are presented, with emphasis on the two most widely implemented methods: determining solubility in fluids aspirated from the human gastrointestinal tract, and determining solubility in so-called biorelevant media, composed to simulate these fluids. The ability of the biorelevant media to predict solubility in human aspirates and to predict plasma profiles is illustrated with case examples.